Plants having increased tolerance to herbicides

ABSTRACT

The present invention refers to a method for controlling undesired vegetation at a plant cultivation site, the method comprising the steps of providing, at said site, a plant that comprises at least one nucleic acid comprising a nucleotide sequence encoding protoporphyrinogen oxidase (PPO) which is resistant or tolerant to a PPO-inhibiting herbicide by applying to said site an effective amount of said herbicide. The invention further refers to plants comprising wild-type or mutated PPO enzymes, and methods of obtaining such plants.

FIELD OF THE INVENTION

The present invention relates in general to methods for conferring onplants agricultural level tolerance to herbicides. Particularly, theinvention refers to plants having an increased tolerance toPPO-inhibiting herbicides. More specifically, the present inventionrelates to methods and plants obtained by mutagenesis and cross-breedingand transformation that have an increased tolerance to PPO-inhibitingherbicides.

BACKGROUND OF THE INVENTION

Herbicides that inhibit protoporphyrinogen oxidase (hereinafter referredto as Protox or PPO; EC:1.3.3.4), a key enzyme in the biosynthesis ofprotoporphyrin IX, have been used for selective weed control since the1960s. PPO catalyzes the last common step in chlorophyll and hemebiosynthesis which is the oxidation of protoporphyrinogen IX toprotoporphyrin IX. (Matringe et al. 1989. Biochem. 1. 260: 231).PPO-inhibiting herbicides include many different structural classes ofmolecules (Duke et al. 1991. Weed Sci. 39: 465; Nandihalli et al. 1992.Pesticide Biochem. Physiol. 43: 193; Matringe et al. 1989. FEBS Lett.245: 35; Yanase and Andoh. 1989. Pesticide Biochem. Physiol. 35: 70).These herbicidal compounds include the diphenylethers {e.g. lactofen,(+-)-2-ethoxy-1-methyl-2-oxoethyl5-{2-chloro-4-(trifluoromethyl)phenoxy}-2-nitrobenzoate; acifluorfen,5-{2-chloro-4-(trifluoromethyl)phenoxy}-2-nitrobenzoic acid; its methylester; or oxyfluorfen,2-chloro-1-(3-ethoxy-4-nitrophenoxy)-4-(trifluorobenzene)}, oxidiazoles,(e.g. oxidiazon,3-{2,4-dichloro-5-(1-methylethoxy)phenyl}-5-(1,1-dimethylethyl)-1,3,4-oxadiazol-2-(3H)-one),cyclic imides (e.g. S-23142,N-(4-chloro-2-fluoro-5-propargyloxyphenyl)-3,4,5,6-tetrahydrophthalimide;chlorophthalim, N-(4-chlorophenyl)-3,4,5,6-tetrahydrophthalimide),phenyl pyrazoles (e.g. TNPP-ethyl, ethyl2-{1-(2,3,4-trichlorophenyl)-4-nitropyrazolyl-5-oxy}propionate; M&B39279), pyridine derivatives (e.g. LS 82-556), and phenopylate and itsO-phenylpyrrolidino- and piperidinocarbamate analogs. Many of thesecompounds competitively inhibit the normal reaction catalyzed by theenzyme, apparently acting as substrate analogs.

Application of PPO-inhibiting herbicides results in the accumulation ofprotoporphyrinogen IX in the chloroplast and mitochondria, which isbelieved to leak into the cytosol where it is oxidized by a peroxidase.When exposed to light, protoporphyrin IX causes formation of singletoxygen in the cytosol and the formation of other reactive oxygenspecies, which can cause lipid peroxidation and membrane disruptionleading to rapid cell death (Lee et al. 1993. Plant Physiol. 102: 881).

Not all PPO enzymes are sensitive to herbicides which inhibit plant PPOenzymes. Both the Escherichia coli and Bacillus subtilis PPO enzymes(Sasarmen et al. 1993. Can. J. Microbiol. 39: 1155; Dailey et al. 1994.J. Biol. Chem. 269: 813) are resistant to these herbicidal inhibitors.Mutants of the unicellular alga Chlamydomonas reinhardtii resistant tothe phenylimide herbicide S-23142 have been reported (Kataoka et al.1990. J. Pesticide Sci. 15: 449; Shibata et al. 1992. In Research inPhotosynthesis, Vol. III, N. Murata, ed. Kluwer:Netherlands. pp.567-70). At least one of these mutants appears to have an altered PPOactivity that is resistant not only to the herbicidal inhibitor on whichthe mutant was selected, but also to other classes of protox inhibitors(Oshio et al. 1993. Z. Naturforsch. 48c: 339; Sato et al. 1994. In ACSSymposium on Porphyric Pesticides, S. Duke, ed. ACS Press: Washington,D.C.). A mutant tobacco cell line has also been reported that isresistant to the inhibitor S-21432 (Che et al. 1993. Z. Naturforsch.48c: 350). Auxotrophic E. coli mutants have been used to confirm theherbicide resistance of cloned plant PPO-inhibiting herbicides.

Three main strategies are available for making plants tolerant toherbicides, i.e. (1) detoxifying the herbicide with an enzyme whichtransforms the herbicide, or its active metabolite, into non-toxicproducts, such as, for example, the enzymes for tolerance to bromoxynilor to basta (EP242236, EP337899); (2) mutating the target enzyme into afunctional enzyme which is less sensitive to the herbicide, or to itsactive metabolite, such as, for example, the enzymes for tolerance toglyphosate (EP293356, Padgette S. R. et al., J. Biol. Chem., 266, 33,1991); or (3) overexpressing the sensitive enzyme so as to producequantities of the target enzyme in the plant which are sufficient inrelation to the herbicide, in view of the kinetic constants of thisenzyme, so as to have enough of the functional enzyme available despitethe presence of its inhibitor. The third strategy was described forsuccessfully obtaining plants which were tolerant to PPO inhibitors (seee.g. U.S. Pat. Nos. 5,767,373 or 5,939,602, and patent family membersthereof.). In addition, US 2010/0100988 and WO 2007/024739 disclosesnucleotide sequences encoding amino acid sequences having enzymaticactivity such that the amino acid sequences are resistant to PPOinhibitor herbicidal chemicals, in particular 3-phenyluracil inhibitorspecific PPO mutants.

WO 2012/080975 discloses plants the tolerance of which to aPPO-inhibiting herbicide named(1,5-dimethyl-6-thioxo-3-(2,2,7-trifluoro-3-oxo-4-(prop-2-ynyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-1,3,5-triazinane-2,4-dione)had been increased by transforming said plants with nucleic acidsencoding mutated PPO mutated enzymes. In particular, WO 2012/080975discloses that the introduction of nucleic acids which code for amutated PPO of an Amaranthus type II PPO in which the Arginine atposition 128 had been replaced by a leucine, alanine, or valine, and thephenylalanine at position 420 had been replaced by a methionine,cysteine, isoleucine, leucine, or threonine, confers increasedtolerance/resistance to a benzoxazinone-derivative herbicide. WO2013/189984 discloses plants the tolerance of which to PPO inhibitorshad been increased by transforming said plants with nucleic acidsencoding mutated PPO enzymes, in which the Leucine corresponding toposition 397 of an Amaranthus type II PPO had been replaced, and thephenylalanine corresponding to position 420 of an Amaranthus type II PPOhad been replaced. WO2015/022636 discloses plants the tolerance of whichto PPO inhibitors had been increased by transforming said plants withnucleic acids encoding mutated PPO enzymes, in which the Argininecorresponding to position 128 of an Amaranthus type II PPO had beenreplaced, and the phenylalanine corresponding to position 420 of anAmaranthus type II PPO had been replaced, but the replacement occurredwith amino acids, which are different from those disclosed in WO2012/080975. WO2015/092706 describes PPO polypeptides from a pluralityof organisms, which PPO polypeptides had been mutated to comprise theadvantageous mutations employed for the Amaranthus type II PPO.WO2015/022640 discloses PPO polypeptides from Alopecurus myosuroides andmutants thereof, which confer tolerance to a broad spectrum of PPOinhibiting herbicides.

The inventors of the present invention have now surprisingly found thatthose types of mutants confer increased tolerance/resistance to a newclass of PPO inhibitors, hereinafter described as uracilpyridines oruracilpyridine herbicides. Thus, to date, the prior art has notdescribed uracilpyridine tolerant plants containing a mutated PPOnucleic acid according to the present invention, which aretolerant/resistant to a broad selection of uracilpyridines.

Therefore, what is needed in the art are crop plants and crop plantshaving increased tolerance to uracilpyridines and containing at leastone wildtype and/or mutated PPO nucleic acid according to the presentinvention. Also needed are methods for controlling weed growth in thevicinity of such crop plants or crop plants. These compositions andmethods would allow for the use of spray over techniques when applyingherbicides to areas containing crop plants or crop plants.

SUMMARY OF THE INVENTION

The problem is solved by the present invention which refers to a methodfor controlling undesired vegetation at a plant cultivation site, themethod comprising the steps of:

-   -   a) providing, at said site, a plant that comprises at least one        nucleic acid comprising a nucleotide sequence encoding a        protoporphyrinogen oxidase (PPO) polypeptide which is resistant        or tolerant to a “PPO inhibiting herbicide”;    -   b) applying to said site an effective amount of said herbicide,        wherein the PPO inhibiting herbicide is a uracilpyridine of        formula (I)

-   -   -   wherein the substituents have the following meanings:        -   R¹ hydrogen, N H, C₁-C₆-alkyl or C₃-C₆-alkynyl;        -   R² hydrogen, C₁-C₆-alkyl or C₁-C₆-haloalkyl;        -   R³ hydrogen or C₁-C₆-alkyl;        -   R⁴ H or halogen;        -   R⁵ halogen, CN, NO₂, NH₂, CF₃ or C(═S)NH₂;        -   R⁶ H, halogen, CN, C₁-C₃-alkyl, C₁-C₃-haloalkyl,            C₁-C₃-alkoxy, C₁-C₃-haloalkoxy, C₁-C₃-alkylthio,            (C₁-C₃-alkyl)amino, di(C₁-C₃-alkyl)amino,            C₁-C₃-alkoxy-C₁-C₃-alkyl, C₁-C₃-alkoxycarbonyl;        -   R⁷ H, halogen, C₁-C₃-alkyl, C₁-C₃-alkoxy;        -   R⁸ OR⁹, SR⁹, NR¹⁰R¹¹, NR⁹OR⁹, NR⁹S(O)₂R¹⁰ or            NR⁹S(O)₂NR¹⁰R¹¹, wherein            -   R⁹ is hydrogen, C₁-C₆-alkyl, C₃-C₆-alkenyl,                C₃-C₆-alkynyl, C₁-C₆-haloalkyl, C₃-C₆-haloalkenyl,                C₃-C₆-haloalkynyl, C₁-C₆-cyanoalkyl,                C₁-C₆-alkoxy-C₁-C₆-alkyl,                C₁-C₆-alkoxy-C₁-C₆-alkoxy-C₁-C₆-alkyl,                di(C₁-C₆-alkoxy)C₁-C₆-alkyl,                C₁-C₆-haloalkoxy-C₁-C₆-alkyl,                C₃-C₆-alkenyloxy-C₁-C₆-alkyl,                C₃-C₆-haloalkenyloxy-C₁-C₆-alkyl,                C₃-C₆-alkenyloxy-C₁-C₆-alkoxy-C₁-C₆-alkyl,                C₁-C₆-alkylthio-C₁-C₆-alkyl,                C₁-C₆-alkylsulfinyl-C₁-C₆-alkyl,                C₁-C₆-alkylsulfonyl-C₁-C₆-alkyl,                C₁-C₆-alkylcarbonyl-C₁-C₆-alkyl,                C₁-C₆-alkoxycarbonyl-C₁-C₆-alkyl,                C₁-C₆-haloalkoxycarbonyl-C₁-C₆-alkyl,                C₃-C₆-alkenyloxycarbonyl-C₁-C₆-alkyl,                C₃-C₆-alkynyloxycarbonyl-C₁-C₆-alkyl, amino,                (C₁-C₆-alkyl)amino, di(C₁-C₆-alkyl)amino,                (C₁-C₆-alkylcarbonyl)amino, amino-C₁-C₆-alkyl,                (C₁-C₆-alkyl)amino-C₁-C₆-alkyl,                di(C₁-C₆-alkyl)amino-C₁-C₆-alkyl,                aminocarbonyl-C₁-C₆-alkyl,                (C₁-C₆-alkyl)aminocarbonyl-C₁-C₆-alkyl,                di(C₁-C₆-alkyl)aminocarbonyl-C₁-C₆-alkyl,                -   —N═CR¹²R¹³, wherein R¹² and R¹³ independently of one                    another are H, C₁-C₄-alkyl or phenyl;                -   C₃-C₆-cycloalkyl, C₃-C₆-cycloalkyl-C₁-C₆-alkyl,                    C₃-C₆-heterocyclyl, C₃-C₆-heterocyclyl-C₁-C₆-alkyl,                    phenyl, phenyl-C₁-C₄-alkyl or a 5- or 6 membered                    heteroaryl,                -    wherein each cycloalkyl, heterocyclyl, phenyl or                    heteroaryl ring can be substituted by one to four                    substituents selected from R¹⁴ or a 3- to 7-membered                    carbocyclus,                -    which carbocyclus optionally has in addition to                    carbon atoms one or two ring members selected from                    the group consisting of —N(R¹²)—, —N═N—, —C(═O)—,                    —O— and —S—, and                -    which carbocyclus is optionally substituted with                    one to four substituents selected from R¹⁴;                -    wherein R¹⁴ is halogen, NO₂, CN, C₁-C₄-alkyl,                    C₁-C₄-haloalkyl, C₁-C₄-alkoxy or                    C₁-C₄-alkoxycarbonyl;            -   R¹⁰, R¹¹ independently of one another are R⁹, or                together form a 3- to 7-membered carbocyclus,                -   which carbocyclus optionally has in addition to                    carbon atoms one or two ring members selected from                    the group consisting of —N(R¹²)—, —N═N—, —C(═O)—,                    —O— and —S—, and                -   which carbocyclus is optionally substituted with one                    to four substituents selected from R¹⁴;        -   n 1 to 3;        -   Q CH₂, O, S, SO, SO₂, NH or (C₁-C₃-alkyl)N;        -   W O or S;        -   X NH, NCH₃, O or S;        -   Y O or S;        -   Z phenyl, pyridyl, pyridazinyl, pyrimidinyl or pyrazinyl,            each of which is optionally substituted by 1 to 4            substituents selected from the group consisting of halogen,            CN, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy,            C₁-C₆-haloalkoxy;

    -   including their agriculturally acceptable salts or derivatives,        provided the compounds of formula (I) have a carboxyl group

and wherein the effective amount of said herbicide does not kill orinhibit the growth of the herbicide-tolerant plant of a).

In one embodiment, the herbicide resistant or tolerant PPO polypeptidecomprises one or more of the following motifs 1, 2, and/or 3:

-   -   a. Motif 1: SQ[N/K/H]KRYI, wherein the Arg at position 5 within        said motif is substituted by any other amino acid;    -   b. Motif 2: TLGTLFSS, wherein the Leu at position 2, and/or the        Gly at position 3, and/or the Leu at position 5 within said        motif is substituted by any other amino acid;    -   c. Motif 3: [F/Y]TTF[V/I]GG, wherein the Phe at position 4        within said motif is substituted by any other amino acid.

In another embodiment, the herbicide resistant or tolerant PPOpolypeptide comprises a variant of the amino acid sequence of SEQ ID NO:1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38,39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56,57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74,75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92,93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108,109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579, 581, 583, 585,587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607, 609, 611, 613,615, 617, 619, 621, 623, 625, 627, or 637, which variant comprises oneor more of the following substitutions:

-   -   a. the amino acid corresponding to Arg128 of SEQ ID NO: 1 is        substituted by any other amino acid.    -   b. The amino acid corresponding to Gly211 of SEQ ID NO: 1 is        substituted by any other amino acid    -   c. the amino acid corresponding to Leu397 of SEQ ID NO: 1 is        substituted by any other amino acid.    -   d. the amino acid corresponding to Gly398 of SEQ ID NO: 1 is        substituted by any other amino acid    -   e. the amino acid corresponding to Leu400 of SEQ ID NO: 1 is        substituted by any other amino acid    -   f. the amino acid corresponding to Phe420 of SEQ ID NO: 1 is        substituted by any other amino acid.

In still another embodiment, the herbicide resistant or tolerant PPOpolypeptide comprises the amino acid sequence of SEQ ID NO: 265, 266,267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280,281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294,295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308,309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322,323, 324, 325, 326, 327 328, 329, 330, 331, 332, 333, 334, 335, 336,337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350,351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364,365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378,379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392,393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406,407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420,421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434,435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448,449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462,463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476,477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490,491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504,505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518,519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532,533, 534, 535, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546,547, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, 560,561, 562, 563, 564, 565, or a variant thereof.

In still another embodiment, the herbicide resistant or tolerant PPOpolypeptide comprises the amino acid sequence of SEQ ID NO: 240, 241,242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255,256, 257, 258, 259, 260, 261, 262,or 264.

Another object refers to a method of identifying a nucleotide sequenceencoding a mutated PPO which is resistant or tolerant to auracilpyridine herbicide, the method comprising:

-   -   a) generating a library of mutated PPO-encoding nucleic acids,    -   b) screening a population of the resulting mutated PPO-encoding        nucleic acids by expressing each of said nucleic acids in a cell        or plant and treating said cell or plant with a uracilpyridine,    -   c) comparing the uracilpyridine herbicide-tolerance levels        provided by said population of mutated PPO encoding nucleic        acids with the uracilpyridine-tolerance level provided by a        control PPO-encoding nucleic acid,    -   d) selecting at least one mutated PPO-encoding nucleic acid that        provides a significantly increased level of tolerance to a        uracilpyridine as compared to that provided by the control        PPO-encoding nucleic acid.

In a preferred embodiment, the mutated PPO-encoding nucleic acidselected in step d) provides at least 2-fold as much tolerance to auracilpyridine as compared to that provided by the control PPO-encodingnucleic acid.

The resistance or tolerance can be determined by generating a transgenicplant comprising a nucleic acid sequence of the library of step a) andcomparing said transgenic plant with a control plant.

Another object refers to a method of identifying a plant or algaecontaining a nucleic acid encoding a mutated PPO which is resistant ortolerant to a uracilpyridine, the method comprising:

-   -   a) identifying an effective amount of a uracilpyridine in a        culture of plant cells or green algae.    -   b) treating said plant cells or green algae with a mutagenizing        agent,    -   c) contacting said mutagenized cells population with an        effective amount of uracilpyridine herbicide, identified in a),    -   d) selecting at least one cell surviving these test conditions,    -   e) PCR-amplification and sequencing of PPO genes from cells        selected in d) and comparing such sequences to wild-type PPO        gene sequences, respectively.

In a preferred embodiment, the mutagenizing agent isethylmethanesulfonate.

In another embodiment, the invention refers to a plant cell transformedby and expressing a wild-type or a mutated PPO nucleic acid according tothe present invention or a plant which has been mutated to obtain aplant expressing, preferably over-expressing a wild-type or a mutatedPPO nucleic acid according to the present invention, wherein expressionof said nucleic acid in the plant cell results in increased resistanceor tolerance to a uracilpyridine as compared to a wild type variety ofthe plant cell.

In another embodiment, the invention refers to a plant that expresses amutagenized or recombinant mutated PPO polypeptide, and wherein saidmutated PPO confers upon the plant increased uracilpyridine tolerance ascompared to the corresponding wild-type variety of the plant whenexpressed therein.

In another embodiment, the invention refers to a plant comprising aplant cell according to the present invention, wherein expression of thenucleic acid in the plant results in the plant's increased resistance touracilpyridine herbicide as compared to a wild type variety of theplant.

The plants of the present invention can be transgenic or non-transgenic.

Preferably, the expression of the nucleic acid of the invention in theplant results in the plant's increased resistance to uracilpyridineherbicides as compared to a wild type variety of the plant.

In another embodiment, the invention refers to a method for growing theplant according to the present invention while controlling weeds in thevicinity of said plant, said method comprising the steps of:

-   -   a) growing said plant; and    -   b) applying a herbicide composition comprising a uracilpyridine        herbicide to the plant and weeds, wherein the herbicide normally        inhibits protoporphyrinogen oxidase, at a level of the herbicide        that would inhibit the growth of a corresponding wild-type        plant.

In another embodiment, the invention refers to a seed produced by atransgenic plant comprising a plant cell of the present invention, or toa seed produced by the non-transgenic plant that expresses a mutagenizedPPO polypeptide, wherein the seed is true breeding for an increasedresistance to a uracilpyridine herbicide as compared to a wild typevariety of the seed.

In another embodiment, the invention refers to a method of producing atransgenic plant cell with an increased resistance to a uracilpyridineherbicide as compared to a wild type variety of the plant cellcomprising, transforming the plant cell with an expression cassettecomprising a wild-type or a mutated PPO nucleic acid.

In another embodiment, the invention refers to a method of producing atransgenic plant comprising, (a) transforming a plant cell with anexpression cassette comprising a wild-type or a mutated PPO nucleicacid, and (b) generating a plant with an increased resistance touracilpyridine herbicide from the plant cell.

Preferably, the expression cassette further comprises a transcriptioninitiation regulatory region and a translation initiation regulatoryregion that are functional in the plant.

In another embodiment, the invention relates to using the mutated PPO ofthe invention as selectable marker. The invention provides a method ofidentifying or selecting a transformed plant cell, plant tissue, plantor part thereof comprising a) providing a transformed plant cell, planttissue, plant or part thereof, wherein said transformed plant cell,plant tissue, plant or part thereof comprises an isolated nucleic acidencoding a mutated PPO polypeptide of the invention as describedhereinafter, wherein the polypeptide is used as a selection marker, andwherein said transformed plant cell, plant tissue, plant or part thereofmay optionally comprise a further isolated nucleic acid of interest; b)contacting the transformed plant cell, plant tissue, plant or partthereof with at least one PPO-inhibiting inhibiting compound; c)determining whether the plant cell, plant tissue, plant or part thereofis affected by the inhibitor or inhibiting compound; and d) identifyingor selecting the transformed plant cell, plant tissue, plant or partthereof.

The invention is also embodied in purified mutated PPO proteins thatcontain the mutations described herein, which are useful in molecularmodeling studies to design further improvements to herbicide tolerance.Methods of protein purification are well known, and can be readilyaccomplished using commercially available products or specially designedmethods, as set forth for example, in Protein Biotechnology, Walsh andHeadon (Wiley, 1994).

In another embodiment, the invention relates to a combination useful forweed control, comprising (a) a polynucleotide encoding a mutated PPOpolypeptide according to the present invention, which polynucleotide iscapable of being expressed in a plant to thereby provide to that planttolerance to a uracilpyridine herbicide; and (b) a uracilpyridineherbicide.

In another embodiment, the invention relates to a process for preparinga combination useful for weed control comprising (a) providing apolynucleotide encoding a mutated PPO polypeptide according to thepresent invention, which polynucleotide is capable of being expressed ina plant to thereby provide to that plant tolerance to a uracilpyridineherbicide; and (b) providing a uracilpyridine herbicide.

In a preferred embodiment, said step of providing a polynucleotidecomprises providing a plant containing the polynucleotide.

In another preferred embodiment, said step of providing a polynucleotidecomprises providing a seed containing the polynucleotide.

In another preferred embodiment, said process further comprises a stepof applying the uracilpyridine herbicide to the seed.

In another embodiment, the invention relates to the use of a combinationuseful for weed control, comprising (a) a polynucleotide encoding amutated PPO polypeptide according to the present invention, whichpolynucleotide is capable of being expressed in a plant to therebyprovide to that plant tolerance to a uracilpyridine herbicide; and (b) auracilpyridine herbicide, to control weeds at a plant cultivation site.

BRIEF DESCRIPTION OF THE DRAWINGS

(NB: full name of used uracilpyridines is given in the Example section)FIG. 1: Rice plants 7 days after treatment with 3.125 g AI/ha ofUracilpyridine 4. A) wild-type, B) R139L mutant, C) R139G mutant, D)G225R mutant, E) G420A mutant, F) F442L mutant, G) F442I mutant, H)F442V mutant, I) L419 mutant, J) L422F mutant

FIG. 2: SRice plants 7 days after treatment with 6.25 g AI/ha ofUracilpyridine 2. A) wild-type, B) R139L mutant, C) R139G mutant, D)G225R mutant, E) G420A mutant, F) F442L mutant, G) F442I mutant, H)F442V mutant, 1) L419 mutant, J) L422F mutant.

FIG. 3: Response of rice containing mutations in the OsPPO2 gene andwild-type rice to application of Uracilpyridine 4. Each bar representsthe average of up to four plants. Phytotoxicity was assessed 7 daysafter herbicide application. ***P-value <0.001, **P-value<0.01,*P-value<0.05 as calculated by ANOVA using a QuasiPoisson distribution

FIG. 4: Response of rice containing mutations in the OsPPO2 gene andwild-type rice to application of Uracilpyridine 2. Each bar representsthe average of up to four plants. Phytotoxicity was assessed 7 daysafter herbicide application. ***P-value <0.001, **P-value<0.01,*P-value<0.05 as calculated by ANOVA using a QuasiPoisson distribution.

Figure: Transgenic T2 Arabidopsis plants harboring Arabidopsis PPOtolerance trait, sprayed post in the greenhouse with the followingamounts (80, 30, 10, 5, 1 g/ha from right to left) of Uracilpyridine+1%(v/v) MSO. Pictures taken 14 Days After Treatment (DAT). A) is testedwith Uracilpyridine 4, B) is tested with Uracilpyridine 5, C) is testedwith Uracilpyridine 2, D) is tested with Uracilpyridine 3.

1=non-transformed Arabidopsis plants

2=Transformants with Arabidopsis PPO1 wildtype

3=Transformants with Arabidopsis PPO1 double mutant S305L_Y426M

FIG. 6: Transgenic T2 Arabidopsis plants harboring various PPO tolerancetrait, sprayed post in the greenhouse with the following amounts (200,100, 50 g/ha) of Uracilpyridine+1% (v/v) MSO. Pictures taken 14 DaysAfter Treatment (DAT). A) is tested with Uracilpyridine 2, B) is testedwith Uracilpyridine 4, C) is tested with Uracilpyridine 1, D) is testedwith Uracilpyridine 2.

1=non-transformed Arabidopsis plants

2=transformed with AMATU_PPO2_TPL_hemG (event R) (SEQ ID NO: 246)

3=transformed with AMATU_PPO2_TPL_hemG (event Q) (SEQ ID NO: 246)

4=transformed with ALOMY_PPO2_TP_hemG (SEQ ID NO: 248)

5=transformed with ALOMY_PPO2_R137L_F438V

6=transformed with ALOMY_PPO2_TPL_AMATU_PPO2_R128M_F420I (SEQ ID NO:258)

7=transformed with AMATU_PPO2_R128M_F420 I

8=transformed with AMATU_PPO2_R128A_F420M

FIG. 7: Transgenic Corn plants harboring a PPO inhibitor tolerancetrait, sprayed post at the V5 leaf stage with 100 g/ha of Uracilpyridine2+1% (v/v) MSO. Evaluation performed 14 Days After Treatment (DAT) andis shown as injury (%) relative to non-transgenic treated plants.Application performed on corn in V5 leaf stage with 100 g/haUracilpyridine 2. Picture taken at 2 DAT

1=Corn transformed with AMATU_PPO2_R128A_F420L

2=Corn transformed with AMATU_PPO2_R128A_F420

3=non-transformed corn plants

FIG. 8: Transgenic T3 Soybean plants harboring a PPO inhibitor tolerancetrait, sprayed post at the V3 leaf stage with 100 g/ha of Uracilpyridine2+1% (v/v) MSO. Evaluation performed 14 Days After Treatment (DAT) andis shown as injury (%) relative to non-transgenic treated plants.Application performed on soy at V3 leaf stage with 100 g/hauracilpyridine 2. Picture taken at 2 DAT

1=Soy transformed with AMATU_PPO2_R128A, F420I

2=Soy transformed with AMATU_PPO2_L397E, F420V

3=Soy transformed with AMATU_PPO2_L397E, F420M

4=Soy transformed with AMATU_PPO2_L397Q, F420M

5=non-transformed soy plants

FIG. 9: Transgenic T4 Soybean plants harboring a PPO inhibitor tolerancetrait, sprayed with 25 g/ha (Panels A-B), 50 g/ha (Panels C-D), 100 g/ha(Panels E-F) of Uracilpyridine 10+1% (v/v) MSO. Evaluation and picturestaken 7 Days After Treatment. Application performed on soybean 14 daysafter sowing. Panels A, C, & E each show plants harboring a PPO traitcontaining R128A+F420L, R128A+F420I AMTU PPO2 variants as well asuntransformed soybean (last column). Panels B, D, & F each show plantsharboring a PPO trait containing L397Q+F420V and L397E+F420M AMTU PPO2variants.

FIG. 10: Transgenic T4 Soybean plants harboring a PPO inhibitortolerance trait, sprayed with 25 g/ha (Panels A-B), 50 g/ha (PanelsC-D), 100 g/ha (Panels E-F) of Uracilpyridine 20+1% (v/v) MSO.Evaluation and pictures taken 7 Days After Treatment. Applicationperformed on soybean 14 days after sowing. Panels A, C, & E each showplants harboring a PPO trait containing R128A+F420L, R128A+F420I AMTUPPO2 variants as well as untransformed soybean (last column). Panels B,D, & F each show plants harboring a PPO trait containing L397Q+F420V andL397E+F420M AMTU PPO2 variants.

FIG. 11: Transgenic T4 Soybean plants harboring a PPO inhibitortolerance trait, sprayed with 25 g/ha (Panels A-B), 50 g/ha (PanelsC-D), 100 g/ha (Panels E-F) of Uracilpyridine 21+1% (v/v) MSO.Evaluation and pictures taken 7 Days After Treatment. Applicationperformed on soybean 14 days after sowing. Panels A, C, & E each showplants harboring a PPO trait containing R128A+F420L, R128A+F420I AMTUPPO2 variants as well as untransformed soybean (last column). Panels B,D, & F each show plants harboring a PPO trait containing L397Q+F420V andL397E+F420M AMTU PPO2 variants.

FIG. 12: Transgenic T4 Soybean plants harboring a PPO inhibitortolerance trait, sprayed with 25 g/ha (Panels A-B), 50 g/ha (PanelsC-D), 100 g/ha (Panels E-F) of Uracilpyridine 22+1% (v/v) MSO.Evaluation and pictures taken 7 Days After Treatment. Applicationperformed on soybean 14 days after sowing. Panels A, C, & E each showplants harboring a PPO trait containing R128A+F420L, R128A+F420I AMTUPPO2 variants as well as untransformed soybean (last column). Panels B,D, & F each show plants harboring a PPO trait containing L397Q+F420V andL397E+F420M AMTU PPO2 variants.

DETAILED DESCRIPTION

The articles “a” and “an” are used herein to refer to one or more thanone (i.e., to at least one) of the grammatical object of the article. Byway of example, “an element” means one or more elements.

As used herein, the word “comprising,” or variations such as “comprises”or “comprising,” will be understood to imply the inclusion of a statedelement, integer or step, or group of elements, integers or steps, butnot the exclusion of any other element, integer or step, or group ofelements, integers or steps.

The inventors of the present invention have found, that the tolerance orresistance of a plant to a uracilpyridine herbicide could be remarkablyincreased by overexpressing a nucleic acid encoding PPO polypeptidesdescribed hereinafter.

The present invention refers to a method for controlling undesiredvegetation at a plant cultivation site, the method comprising the stepsof:

-   -   a) providing, at said site, a plant that comprises at least one        nucleic acid comprising a nucleotide sequence encoding a        protoporphyrinogen oxidase (mutated PPO) which is resistant or        tolerant to a PPO-inhibiting herbicide as defined hereinafter,    -   b) applying to said site an effective amount of said herbicide,

wherein the PPO inhibiting herbicide is a uracilpyridine of formula (I)

-   -   wherein the substituents have the following meanings:    -   R¹ hydrogen, NH₂, C₁-C₆-alkyl or C₃-C₆-alkynyl;    -   R² hydrogen, C₁-C₆-alkyl or C₁-C₆-haloalkyl;    -   R³ hydrogen or C₁-C₆-alkyl;    -   R⁴ H or halogen;    -   R⁵ halogen, CN, NO₂, NH₂, CF₃ or C(═S)NH₂;    -   R⁶ H, halogen, CN, C₁-C₃-alkyl, C₁-C₃-haloalkyl, C₁-C₃-alkoxy,        C₁-C₃-haloalkoxy, C₁-C₃-alkylthio, (C₁-C₃-alkyl)amino,        di(C₁-C₃-alkyl)amino, C₁-C₃-alkoxy-C₁-C₃-alkyl,        C₁-C₃-alkoxycarbonyl;    -   R⁷ H, halogen, C₁-C₃-alkyl, C₁-C₃-alkoxy;    -   R⁸ OR⁹, SR⁹, NR¹⁰R¹¹, NR⁹OR⁹, NR⁹S(O)₂R¹⁰ or NR⁹S(O)₂NR¹⁰R¹¹,        wherein        -   R⁹ is hydrogen, C₁-C₆-alkyl, C₃-C₆-alkenyl, C₃-C₆-alkynyl,            C₁-C₆-haloalkyl, C₃-C₆-haloalkenyl, C₃-C₆-haloalkynyl,            C₁-C₆-cyanoalkyl, C₁-C₆-alkoxy-C₁-C₆-alkyl,            C₁-C₆-alkoxy-C₁-C₆-alkoxy-C₁-C₆-alkyl,            di(C₁-C₆-alkoxy)C₁-C₆-alkyl, C₁-C₆-haloalkoxy-C₁-C₆-alkyl,            C₃-C₆-alkenyloxy-C₁-C₆-alkyl,            C₃-C₆-haloalkenyloxy-C₁-C₆-alkyl,            C₃-C₆-alkenyloxy-C₁-C₆-alkoxy-C₁-C₆-alkyl,            C₁-C₆-alkylthio-C₁-C₆-alkyl,            C₁-C₆-alkylsulfinyl-C₁-C₆-alkyl,            C₁-C₆-alkylsulfonyl-C₁-C₆-alkyl,            C₁-C₆-alkylcarbonyl-C₁-C₆-alkyl,            C₁-C₆-alkoxycarbonyl-C₁-C₆-alkyl,            C₁-C₆-haloalkoxycarbonyl-C₁-C₆-alkyl,            C₃-C₆-alkenyloxycarbonyl-C₁-C₆-alkyl,            C₃-C₆-alkynyloxycarbonyl-C₁-C₆-alkyl, amino,            (C₁-C₆-alkyl)amino, di(C₁-C₆-alkyl)amino,            (C₁-C₆-alkylcarbonyl)amino, amino-C₁-C₆-alkyl,            (C₁-C₆-alkyl)amino-C₁-C₆-alkyl,            di(C₁-C₆-alkyl)amino-C₁-C₆-alkyl, aminocarbonyl-C₁-C₆-alkyl,            (C₁-C₆-alkyl)aminocarbonyl-C₁-C₆-alkyl,            di(C₁-C₆-alkyl)aminocarbonyl-C₁-C₆-alkyl,            -   —N═CR¹²R¹³, wherein R¹² and R¹³ independently of one                another are H, C₁-C₄-alkyl or phenyl;            -   C₃-C₆-cycloalkyl, C₃-C₆-cycloalkyl-C₁-C₆-alkyl,                C₃-C₆-heterocyclyl, C₃-C₆-heterocyclyl-C₁-C₆-alkyl,                phenyl, phenyl-C₁-C₄-alkyl or a 5- or 6 membered                heteroaryl,                -   wherein each cycloalkyl, heterocyclyl, phenyl or                    heteroaryl ring can be substituted by one to four                    substituents selected from R¹⁴ or a 3- to 7-membered                    carbocyclus,                -    which carbocyclus optionally has in addition to                    carbon atoms one or two ring members selected from                    the group consisting of —N(R¹²)—, —N═N—, —C(═O)—,                    —O— and —S—, and                -    which carbocyclus is optionally substituted with                    one to four substituents selected from R¹⁴;                -    wherein R¹⁴ is halogen, NO₂, CN, C₁-C₄-alkyl,                    C₁-C₄-haloalkyl, C₁-C₄-alkoxy or                    C₁-C₄-alkoxycarbonyl;        -   R¹⁰, R¹¹ independently of one another are R⁹, or together            form a 3- to 7-membered carbocyclus,            -   which carbocyclus optionally has in addition to carbon                atoms one or two ring members selected from the group                consisting of —N(R¹²)—, —N═N—, —C(═O)—, —O— and —S—, and                which carbocyclus is optionally substituted with one to                four substituents selected from R¹⁴;    -   n 1 to 3;    -   Q CH₂, O, S, SO, SO₂, NH or (C₁-C₃-alkyl)N;    -   W O or S;    -   X NH, NCH₃, O or S;    -   Y O or S;    -   Z phenyl, pyridyl, pyridazinyl, pyrimidinyl or pyrazinyl, each        of which is optionally substituted by 1 to 4 substituents        selected from the group consisting of halogen, CN, C₁-C₆-alkyl,        C₁-C₆-haloalkyl, C₁-C₆-alkoxy, C₁-C₆-haloalkoxy;    -   including their agriculturally acceptable salts or derivatives,        provided the compounds of formula (I) have a carboxyl group.

The term “control of undesired vegetation” is to be understood asmeaning the killing of weeds and/or otherwise retarding or inhibitingthe normal growth of the weeds. Weeds, in the broadest sense, areunderstood as meaning all those plants which grow in locations wherethey are undesired, e.g. (crop) plant cultivation sites. The weeds ofthe present invention include, for example, dicotyledonous andmonocotyledonous weeds. Dicotyledonous weeds include, but are notlimited to, weeds of the genera: Sinapis, Lepidium, Galium, Stellaria,Matricaria, Anthemis, Galinsoga, Chenopodium, Urtica, Senecio,Amaranthus, Portulaca, Xanthium, Convolvulus, Ipomoea, Polygonum,Sesbania, Ambrosia, Cirsium, Carduus, Sonchus, Solanum, Rorippa, Rotala,Lindernia, Lamium, Veronica, Abutilon, Emex, Datura, Viola, Galeopsis,Papaver, Centaurea, Trifolium, Ranunculus, and Taraxacum.Monocotyledonous weeds include, but are not limited to, weeds of thegenera: Echinochloa, Setaria, Panicum, Digitaria, Phleum, Poa, Festuca,Eleusine, Brachiaria, Lolium, Bromus, Avena, Cyperus, Sorghum,Agropyron, Cynodon, Monochoria, Fimbristyslis, Sagittaria, Eleocharis,Scirpus, Paspalum, Ischaemum, Sphenoclea, Dactyloctenium, Agrostis,Alopecurus, and Apera. In addition, the weeds of the present inventioncan include, for example, crop plants that are growing in an undesiredlocation. For example, a volunteer maize plant that is in a field thatpredominantly comprises soybean plants can be considered a weed, if themaize plant is undesired in the field of soybean plants.

The term “plant” is used in its broadest sense as it pertains to organicmaterial and is intended to encompass eukaryotic organisms that aremembers of the Kingdom Plantae, examples of which include but are notlimited to vascular plants, vegetables, grains, flowers, trees, herbs,bushes, grasses, vines, ferns, mosses, fungi and algae, etc, as well asclones, offsets, and parts of plants used for asexual propagation (e.g.cuttings, pipings, shoots, rhizomes, underground stems, clumps, crowns,bulbs, corms, tubers, rhizomes, plants/tissues produced in tissueculture, etc.). The term “plant” further encompasses whole plants,ancestors and progeny of the plants and plant parts, including seeds,shoots, stems, leaves, roots (including tubers), flowers, florets,fruits, pedicles, peduncles, stamen, anther, stigma, style, ovary,petal, sepal, carpel, root tip, root cap, root hair, leaf hair, seedhair, pollen grain, microspore, cotyledon, hypocotyl, epicotyl, xylem,phloem, parenchyma, endosperm, a companion cell, a guard cell, and anyother known organs, tissues, and cells of a plant, and tissues andorgans, wherein each of the aforementioned comprise the gene/nucleicacid of interest. The term “plant” also encompasses plant cells,suspension cultures, callus tissue, embryos, meristematic regions,gametophytes, sporophytes, pollen and microspores, again wherein each ofthe aforementioned comprises the gene/nucleic acid of interest.

Plants that are particularly useful in the methods of the inventioninclude all plants which belong to the superfamily Viridiplantae, inparticular monocotyledonous and dicotyledonous plants including fodderor forage legumes, ornamental plants, food crops, trees or shrubsselected from the list comprising Acer spp., Actinidia spp., Abelmoschusspp., Agave sisalana, Agropyron spp., Agrostis stolonifera, Allium spp.,Amaranthus spp., Ammophila arenaria, Ananas comosus, Annona spp., Apiumgraveolens, Arachis spp, Artocarpus spp., Asparagus officinalis, Avenaspp. (e.g. Avena sativa, Avena fatua, Avena byzantina, Avena fatua var.sativa, Avena hybrida), Averrhoa carambola, Bambusa sp., Benincasahispida, Bertholletia excelsea, Beta vulgaris, Brassica spp. (e.g.Brassica napus, Brassica rapa ssp. [canola, oilseed rape, turnip rape]),Cadaba farinosa, Camellia sinensis, Canna indica, Cannabis sativa,Capsicum spp., Carex elata, Carica papaya, Carissa macrocarpa, Caryaspp., Carthamus tinctorius, Castanea spp., Ceiba pentandra, Cichoriumendivia, Cinnamomum spp., Citrullus lanatus, Citrus spp., Cocos spp.,Coffea spp., Colocasia esculenta, Cola spp., Corchorus sp., Coriandrumsativum, Corylus spp., Crataegus spp., Crocus sativus, Cucurbita spp.,Cucumis spp., Cynara spp., Daucus carota, Desmodium spp., Dimocarpuslongan, Dioscorea spp., Diospyros spp., Echinochloa spp., Elaeis (e.g.Elaeis guineensis, Elaeis oleifera), Eleusine coracana, Eragrostis tef,Erianthus sp., Eriobotrya japonica, Eucalyptus sp., Eugenia uniflora,Fagopyrum spp., Fagus spp., Festuca arundinacea, Ficus carica,Fortunella spp., Fragaria spp., Ginkgo biloba, Glycine spp. (e.g.Glycine max, Soja hispida or Soja max), Gossypium hirsutum, Helianthusspp. (e.g. Helianthus annuus), Hemerocallis fulva, Hibiscus spp.,Hordeum spp. (e.g. Hordeum vulgare), Ipomoea batatas, Juglans spp.,Lactuca sativa, Lathyrus spp., Lens culinaris, Linum usitatissimum,Litchi chinensis, Lotus spp., Luffa acutangula, Lupinus spp., Luzulasylvatica, Lycopersicon spp. (e.g. Lycopersicon esculentum, Lycopersiconlycopersicum, Lycopersicon pyriforme), Macrotyloma spp., Malus spp.,Malpighia emarginata, Mammea americana, Mangifera indica, Manihot spp.,Manilkara zapota, Medicago sativa, Melilotus spp., Mentha spp.,Miscanthus sinensis, Momordica spp., Morus nigra, Musa spp., Nicotianaspp., Olea spp., Opuntia spp., Ornithopus spp., Oryza spp. (e.g. Oryzasativa, Oryza latifolia), Panicum miliaceum, Panicum virgatum,Passiflora edulis, Pastinaca sativa, Pennisetum sp., Persea spp.,Petroselinum crispum, Phalaris arundinacea, Phaseolus spp., Phleumpratense, Phoenix spp., Phragmites australis, Physalis spp., Pinus spp.,Pistacia vera, Pisum spp., Poa spp., Populus spp., Prosopis spp., Prunusspp., Psidium spp., Punica granatum, Pyrus communis, Quercus spp.,Raphanus sativus, Rheum rhabarbarum, Ribes spp., Ricinus communis, Rubusspp., Saccharum spp., Salix sp., Sambucus spp., Secale cereale, Sesamumspp., Sinapis sp., Solanum spp. (e.g. Solanum tuberosum, Solanumintegrifolium or Solanum lycopersicum), Sorghum bicolor, Spinacia spp.,Syzygium spp., Tagetes spp., Tamarindus indica, Theobroma cacao,Trifolium spp., Tripsacum dactyloides, Triticosecale rimpaui, Triticumspp. (e.g. Triticum aestivum, Triticum durum, Triticum turgidum,Triticum hybernum, Triticum macha, Triticum sativum, Triticum monococcumor Triticum vulgare), Tropaeolum minus, Tropaeolum majus, Vacciniumspp., Vicia spp., Vigna spp., Viola odorata, Vitis spp., Zea mays,Zizania palustris, Ziziphus spp., amaranth, artichoke, asparagus,broccoli, Brussels sprouts, cabbage, canola, carrot, cauliflower,celery, collard greens, flax, kale, lentil, oilseed rape, okra, onion,potato, rice, soybean, strawberry, sugar beet, sugar cane, sunflower,tomato, squash, tea and algae, amongst others. According to a preferredembodiment of the present invention, the plant is a crop plant. Examplesof crop plants include inter ala soybean, sunflower, canola, alfalfa,rapeseed, cotton, tomato, potato or tobacco. Further preferably, theplant is a monocotyledonous plant, such as sugarcane. Furtherpreferably, the plant is a cereal, such as rice, maize, wheat, barley,millet, rye, sorghum or oats.

In a preferred embodiment, the plant has been previously produced by aprocess comprising recombinantly preparing a plant by introducing andover-expressing a wild-type or mutated PPO transgene according to thepresent invention, as described in greater detail hereinfter.

In another preferred embodiment, the plant has been previously producedby a process comprising in situ mutagenizing plant cells, to obtainplant cells which express a mutated PPO.

As disclosed herein, the nucleic acids of the invention find use inenhancing the herbicide tolerance of plants that comprise in theirgenomes a gene encoding a herbicide-tolerant wild-type or mutated PPOprotein. Such a gene may be an endogenous gene or a transgene, asdescribed hereinafter.

Therefore, in another embodiment the present invention refers to amethod of increasing or enhancing the uracilpyridine herbicide toleranceor resistance of a plant, the method comprising overexpressing a nucleicacid encoding a PPO polypeptide which comprises one or more of thefollowing motifs 1, 2, and/or 3:

-   -   a. Motif 1: SQ[N/K/H]KRYI, wherein the Arg at position 5 within        said motif is substituted by any other amino acid;    -   b. Motif 2: TLGTLFSS, wherein the Leu at position 2 and/or the        Gly at position 3, and/or the Leu at position 5 within said        motif is substituted by any other amino acid;    -   c. Motif 3: [F/Y]TTF[V/I]GG, wherein the Phe at position 4        within said motif is substituted by any other amino acid.

In another embodiment the present invention refers to a method ofincreasing or enhancing the uracilpyridine herbicide tolerance orresistance of a plant, the method comprising overexpressing a nucleicacid encoding a herbicide resistant or tolerant PPO polypeptide whichcomprises a variant of the amino acid sequence of SEQ ID NO: 1, 2, 3, 4,5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41,42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59,60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77,78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95,96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110,111, 112, 113, 114, 115, 116, 117, 577, 579, 581, 583, 585, 587, 589,591, 593, 595, 597, 599, 601, 603, 605, 607, 609, 611, 613, 615, 617,619, 621, 623, 625, 627, or 637, which variant comprises one or more ofthe following substitutions:

-   -   a. the amino acid corresponding to Arg128 of SEQ ID NO: 1 is        substituted by any other amino acid.    -   b. The amino acid corresponding to Gly211 of SEQ ID NO: 1 is        substituted by any other amino acid    -   c. the amino acid corresponding to Leu397 of SEQ ID NO: 1 is        substituted by any other amino acid.    -   d. the amino acid corresponding to Gly398 of SEQ ID NO: 1 is        substituted by any other amino acid    -   e. the amino acid corresponding to Leu400 of SEQ ID NO: 1 is        substituted by any other amino acid    -   f. the amino acid corresponding to Phe420 of SEQ ID NO: 1 is        substituted by any other amino acid.

In another embodiment the present invention refers to a method ofincreasing or enhancing the uracilpyridine herbicide tolerance orresistance of a plant, the method comprising overexpressing a nucleicacid encoding a herbicide resistant or tolerant PPO polypeptide whichcomprises the amino acid sequence of SEQ ID NO: 265, 266, 267, 268, 269,270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283,284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297,298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311,312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325,326, 327328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340,341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354,355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368,369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382,383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396,397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410,411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424,425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438,439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452,453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466,467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480,481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494,495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508,509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522,523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536,537, 538, 539, 540, 541, 542, 543, 544, 545, 546, 547, 548, 549, 550,551, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561, 562, 563, 564,565, or a variant thereof.

In another embodiment the present invention refers to a method ofincreasing or enhancing the uracilpyridine herbicide tolerance orresistance of a plant, the method comprising overexpressing a nucleicacid encoding a herbicide resistant or tolerant PPO polypeptide whichcomprises the amino acid sequence of SEQ ID NO: 240, 241, 242, 243, 244,245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258,259, 260, 261, 262, or 264.

Additionally, in certain embodiments, the nucleic acids of the presentinvention can be stacked with any combination of polynucleotidesequences of interest in order to create plants with a desiredphenotype. For example, the nucleic acids of the present invention maybe stacked with any other polynucleotides encoding polypeptides havingpesticidal and/or insecticidal activity, such as, for example, theBacillus thuringiensis toxin proteins (described in U.S. Pat. Nos.5,366,892; 5,747,450; 5,737,514; 5,723,756; 5,593,881; and Geiser et al(1986) Gene 48: 109),

By way of example, polynucleotides that may be stacked with the nucleicacids of the present invention include nucleic acids encodingpolypeptides conferring resistance to pests/pathogens such as viruses,nematodes, insects or fungi, and the like. Exemplary polynucleotidesthat may be stacked with nucleic acids of the invention includepolynucleotides encoding: polypeptides having pesticidal and/orinsecticidal activity, such as other Bacillus thuringiensis toxicproteins (described in U.S. Pat. Nos. 5,366,892; 5,747,450; 5,737,514;5,723,756; 5,593,881; and Geiser et al., (1986) Gene 48:109), lectins(Van Damme et al. (1994) Plant Mol. Biol. 24:825, pentin (described inU.S. Pat. No. 5,981,722), and the like; traits desirable for disease orherbicide resistance (e.g., fumonisin detoxification genes (U.S. Pat.No. 5,792,931); avirulence and disease resistance genes (Jones et al.(1994) Science 266:789; Martin et al., (1993) Science 262:1432;Mindrinos et al. (1994) Cell 78:1089); acetolactate synthase (ALS)mutants that lead to herbicide resistance such as the S4 and/or Hramutations; glyphosate resistance (e.g.,5-enol-pyrovyl-shikimate-3-phosphate-synthase (EPSPS) gene, described inU.S. Pat. Nos. 4,940,935 and 5,188,642; or the glyphosateN-acetyltransferase (GAT) gene, described in Castle et al. (2004)Science, 304:1151-1154; and in U.S. Patent App. Pub. Nos. 20070004912,20050246798, and 20050060767)); glufosinate resistance (e.g,phosphinothricin acetyl transferase genes PAT and BAR, described in U.S.Pat. Nos. 5,561,236 and 5,276,268); resistance to herbicides includingsulfonyl urea, DHT (2, 4D), and PPO herbicides (e.g., glyphosate acetyltransferase, aryloxy alkanoate dioxygenase, acetolactate synthase, andprotoporphyrinogen oxidase); a cytochrome P450 or variant thereof thatconfers herbicide resistance or tolerance to, inter alia, HPPDherbicides (U.S. patent application Ser. No. 12/156,247; U.S. Pat. Nos.6,380,465; 6,121,512; 5,349,127; 6,649,814; and 6,300,544; and PCTPatent App. Pub. No. WO2007000077); and traits desirable for processingor process products such as high oil (e.g., U.S. Pat. No. 6,232,529);modified oils (e.g., fatty acid desaturase genes (U.S. Pat. No.5,952,544; WO 94/11516)); modified starches (e.g., ADPGpyrophosphorylases (AGPase), starch synthases (SS), starch branchingenzymes (SBE), and starch debranching enzymes (SDBE)); and polymers orbioplastics (e.g., U.S. Pat. No. 5,602,321; beta-ketothiolase,polyhydroxybutyrate synthase, and acetoacetyl-CoA reductase (Schubert etal. (1988) J. Bacteriol. 170:5837-5847) facilitate expression ofpolyhydroxyalkanoates (PHAs)); the disclosures of which are hereinincorporated by reference.

In a preferred embodiment, the plant comprises at least one additionalheterologous nucleic acid comprising a nucleotide sequence encoding aherbicide tolerance enzyme selected, for example, from the groupconsisting of 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS),Glyphosate acetyl transferase (GAT), cytochrome P450 monooxygenase,phosphinothricin acetyltransferase (PAT), Acetohydroxyacid synthase(AHAS; EC 4.1.3.18, also known as acetolactate synthase or ALS),hydroxyphenyl pyruvate dioxygenase (HPPD), Phytoene desaturase (PD) anddicamba degrading enzymes as disclosed in WO 02/068607, orphenoxyaceticacid- and phenoxypropionicacid-derivative degrading enzymesas disclosed in WO 2008141154 or WO 2005107437. The combinationsgenerated can also include multiple copies of any one of thepolynucleotides of interest.

Generally, the term “herbicide” is used herein to mean an activeingredient that kills, controls or otherwise adversely modifies thegrowth of plants. The preferred amount or concentration of the herbicideis an “effective amount” or “effective concentration.” By “effectiveamount” and “effective concentration” is intended an amount andconcentration, respectively, that is sufficient to kill or inhibit thegrowth of a similar, wild-type, plant, plant tissue, plant cell, or hostcell, but that said amount does not kill or inhibit as severely thegrowth of the herbicide-resistant plants, plant tissues, plant cells,and host cells of the present invention. Typically, the effective amountof a herbicide is an amount that is routinely used in agriculturalproduction systems to kill weeds of interest. Such an amount is known tothose of ordinary skill in the art. Herbicidal activity is exhibited byherbicides useful for the present invention when they are applieddirectly to the plant or to the locus of the plant at any stage ofgrowth or before planting or emergence. The effect observed depends uponthe plant species to be controlled, the stage of growth of the plant,the application parameters of dilution and spray drop size, the particlesize of solid components, the environmental conditions at the time ofuse, the specific compound employed, the specific adjuvants and carriersemployed, the soil type, and the like, as well as the amount of chemicalapplied. These and other factors can be adjusted as is known in the artto promote non-selective or selective herbicidal action. Generally, itis preferred to apply the herbicide postemergence to relatively immatureundesirable vegetation to achieve the maximum control of weeds.

By a “herbicide-tolerant” or “herbicide-resistant” plant, it is intendedthat a plant that is tolerant or resistant to at least one herbicide ata level that would normally kill, or inhibit the growth of, a normal orwild-type plant. By “herbicide-tolerant wildtype or mutated PPO protein”or “herbicide-resistant wildtype or mutated PPO protein”, it is intendedthat such a PPO protein displays higher PPO activity, relative to thePPO activity of a wild-type PPO protein, when in the presence of atleast one herbicide that is known to interfere with PPO activity and ata concentration or level of the herbicide that is known to inhibit thePPO activity of the wild-type mutated PPO protein. Furthermore, the PPOactivity of such a herbicide-tolerant or herbicide-resistant mutated PPOprotein may be referred to herein as “herbicide-tolerant” or“herbicide-resistant” PPO activity.

In a particularly preferred embodiment, the herbicides useful for thepresent invention refer uracilpyridines of formula (I)

-   -   wherein the substituents have the following meanings:    -   R¹ hydrogen, NH₂, C₁-C₆-alkyl or C₃-C₆-alkynyl;    -   R² hydrogen, C₁-C₆-alkyl or C₁-C₆-haloalkyl;    -   R³ hydrogen or C₁-C₆-alkyl;    -   R⁴ H or halogen;    -   R⁵ halogen, CN, NO₂, NH₂, CF₃ or C(═S)NH₂;    -   R⁶ H, halogen, CN, C₁-C₃-alkyl, C₁-C₃-haloalkyl, C₁-C₃-alkoxy,        C₁-C₃-haloalkoxy, C₁-C₃-alkylthio, (C₁-C₃-alkyl)amino,        di(C₁-C₃-alkyl)amino, C₁-C₃-alkoxy-C₁-C₃-alkyl,        C₁-C₃-alkoxycarbonyl;    -   R⁷ H, halogen, C₁-C₃-alkyl, C₁-C₃-alkoxy;    -   R⁸ OR⁹, SR⁹, NR¹⁰R¹¹, NR⁹OR⁹, NR⁹S(O)₂R¹⁰ or NR⁹S(O)₂NR¹⁰R¹¹,        wherein        -   R⁹ is hydrogen, C₁-C₆-alkyl, C₃-C₆-alkenyl, C₃-C₆-alkynyl,            C₁-C₆-haloalkyl, C₃-C₆-haloalkenyl, C₃-C₆-haloalkynyl,            C₁-C₆-cyanoalkyl, C₁-C₆-alkoxy-C₁-C₆-alkyl,            C₁-C₆-alkoxy-C₁-C₆-alkoxy-C₁-C₆-alkyl,            di(C₁-C₆-alkoxy)C₁-C₆-alkyl, C₁-C₆-haloalkoxy-C₁-C₆-alkyl,            C₃-C₆-alkenyloxy-C₁-C₆-alkyl,            C₃-C₆-haloalkenyloxy-C₁-C₆-alkyl,            C₃-C₆-alkenyloxy-C₁-C₆-alkoxy-C₁-C₆-alkyl,            C₁-C₆-alkylthio-C₁-C₆-alkyl,            C₁-C₆-alkylsulfinyl-C₁-C₆-alkyl,            C₁-C₆-alkylsulfonyl-C₁-C₆-alkyl,            C₁-C₆-alkylcarbonyl-C₁-C₆-alkyl,            C₁-C₆-alkoxycarbonyl-C₁-C₆-alkyl,            C₁-C₆-haloalkoxycarbonyl-C₁-C₆-alkyl,            C₃-C₆-alkenyloxycarbonyl-C₁-C₆-alkyl,            C₃-C₆-alkynyloxycarbonyl-C₁-C₆-alkyl, amino,            (C₁-C₆-alkyl)amino, di(C₁-C₆-alkyl)amino,            (C₁-C₆-alkylcarbonyl)amino, amino-C₁-C₆-alkyl,            (C₁-C₆-alkyl)amino-C₁-C₆-alkyl,            di(C₁-C₆-alkyl)amino-C₁-C₆-alkyl, aminocarbonyl-C₁-C₆-alkyl,            (C₁-C₆-alkyl)aminocarbonyl-C₁-C₆-alkyl,            di(C₁-C₆-alkyl)aminocarbonyl-C₁-C₆-alkyl,            -   —N═CR¹²R¹³, wherein R¹² and R¹³ independently of one                another are H, C₁-C₄-alkyl or phenyl;            -   C₃-C₆-cycloalkyl, C₃-C₆-cycloalkyl-C₁-C₆-alkyl,                C₃-C₆-heterocyclyl, C₃-C₆-heterocyclyl-C₁-C₆-alkyl,                phenyl, phenyl-C₁-C₄-alkyl or a 5- or 6 membered                heteroaryl,                -   wherein each cycloalkyl, heterocyclyl, phenyl or                    heteroaryl ring can be substituted by one to four                    substituents selected from R¹⁴ or a 3- to 7-membered                    carbocyclus,                -    which carbocyclus optionally has in addition to                    carbon atoms one or two ring members selected from                    the group consisting of —N(R¹²)—, —N═N—, —C(═O)—,                    —O— and —S—, and                -    which carbocyclus is optionally substituted with                    one to four substituents selected from R¹⁴;                -    wherein R¹⁴ is halogen, NO₂, CN, C₁-C₄-alkyl,                    C₁-C₄-haloalkyl, C₁-C₄-alkoxy or                    C₁-C₄-alkoxycarbonyl;        -   R¹⁰, R¹¹ independently of one another are R⁹, or together            form a 3- to 7-membered carbocyclus,            -   which carbocyclus optionally has in addition to carbon                atoms one or two ring members selected from the group                consisting of —N(R¹²)—, —N═N—, —C(═O)—, —O— and —S—, and            -   which carbocyclus is optionally substituted with one to                four substituents selected from R¹⁴;    -   n 1 to 3;    -   Q CH₂, O, S, SO, SO₂, NH or (C₁-C₃-alkyl)N;    -   W O or S;    -   X NH, NCH₃, O or S;    -   Y O or S;    -   Z phenyl, pyridyl, pyridazinyl, pyrimidinyl or pyrazinyl,        -   each of which is optionally substituted by 1 to 4            substituents selected from the group consisting of halogen,            CN, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy,            C₁-C₆-haloalkoxy;    -   including their agriculturally acceptable salts or derivatives,        provided the compounds of formula (I) have a carboxyl group.

If the uracilpyridines of formula (I), the herbicidal compounds B and/orthe safeners C as described herein are capable of forming geometricalisomers, for example E/Z isomers, it is possible to use both, the pureisomers and mixtures thereof, in the compositions according to theinvention.

If the uracilpyridines of formula (I), the herbicidal compounds B and/orthe safeners C as described herein have one or more centres of chiralityand, as a consequence, are present as enantiomers or diastereomers, itis possible to use both, the pure enantiomers and diastereomers andtheir mixtures, in the compositions according to the invention.

Within the substituents of the uracilpyridines of formula (I), insteadof hydrogene also the corresponding isotope deuterium can be used.

If the uracilpyridines of formula (I), the herbicidal compounds B and/orthe safeners C as described herein have ionizable functional groups,they can also be employed in the form of their agriculturally acceptablesalts. Suitable are, in general, the salts of those cations and the acidaddition salts of those acids whose cations and anions, respectively,have no adverse effect on the activity of the active compounds.

Preferred cations are the ions of the alkali metals, preferably oflithium, sodium and potassium, of the alkaline earth metals, preferablyof calcium and magnesium, and of the transition metals, preferably ofmanganese, copper, zinc and iron, further ammonium and substitutedammonium in which one to four hydrogen atoms are replaced byC₁-C₄-alkyl, hydroxy-C₁-C₄-alkyl, C₁-C₄-alkoxy-C₁-C₄-alkyl,hydroxy-C₁-C₄-alkoxy-C₁-C₄-alkyl, phenyl or benzyl, preferably ammonium,methylammonium, isopropylammonium, dimethylammonium, diethylammonium,diisopropylammonium, trimethylammonium, triethylammonium,tris(isopropyl)ammonium, heptylammonium, dodecylammonium,tetradecylammonium, tetramethylammonium, tetraethylammonium,tetrabutylammonium, 2-hydroxyethylammonium (olamine salt),2-(2-hydroxyeth-1-oxy)eth-1-ylammonium (diglycolamine salt),di(2-hydroxyeth-1-yl)ammonium (diolamine salt),tris(2-hydroxyethyl)ammonium (trolamine salt),tris(2-hydroxypropyl)ammonium, benzyltrimethylammonium,benzyltriethylammonium, N,N,N-trimethylethanolammonium (choline salt),furthermore phosphonium ions, sulfonium ions, preferablytri(C₁-C₄-alkyl)sulfonium, such as trimethylsulfonium, and sulfoxoniumions, preferably tri(C₁-C₄-alkyl)sulfoxonium, and finally the salts ofpolybasic amines such as N,N-bis-(3-aminopropyl)methylamine anddiethylenetriamine.

Also preferred cations are the ions of the alkali metals, preferably oflithium, sodium and potassium, of the alkaline earth metals, preferablyof calcium and magnesium, and of the transition metals, preferably ofmanganese, copper, zinc and iron, further ammonium and substitutedammonium in which one to four hydrogen atoms are replaced byC₁-C₄-alkyl, hydroxy-C₁-C₄-alkyl, C₁-C₄-alkoxy-C₁-C₄-alkyl,hydroxy-C₁-C₄-alkoxy-C₁-C₄-alkyl, phenyl or benzyl, preferably ammonium,methylammonium, isopropylammonium, dimethylammonium,diisopropylammonium, trimethylammonium, heptylammonium, dodecylammonium,tetradecylammonium, tetramethylammonium, tetraethylammonium,tetrabutylammonium, 2-hydroxyethylammonium (olamine salt),2-(2-hydroxyeth-1-oxy)eth-1-ylammonium (diglycolamine salt),di(2-hydroxyeth-1-yl)ammonium (diolamine salt),tris(2-hydroxyethyl)ammonium (trolamine salt),tris(2-hydroxypropyl)ammonium, benzyltrimethylammonium,benzyltriethylammonium, N,N,N-trimethylethanolammonium (choline salt),furthermore phosphonium ions, sulfonium ions, preferablytri(C₁-C₄-alkyl)sulfonium, such as trimethylsulfonium, and sulfoxoniumions, preferably tri(C₁-C₄-alkyl)sulfoxonium, and finally the salts ofpolybasic amines such as N,N-bis-(3-aminopropyl)methylamine anddiethylenetriamine.

Anions of useful acid addition salts are primarily chloride, bromide,fluoride, iodide, hydrogensulfate, methylsulfate, sulfate,dihydrogenphosphate, hydrogenphosphate, nitrate, bicarbonate, carbonate,hexafluorosilicate, hexafluorophosphate, benzoate and also the anions ofC₁-C₄-alkanoic acids, preferably formate, acetate, propionate andbutyrate.

Uracilpyridines of formula (I), herbicidal compounds B and/or safeners Cas described herein having a carboxyl group can be employed in the formof the acid, in the form of an agriculturally suitable salt as mentionedabove or else in the form of an agriculturally acceptable derivative,for example as amides, such as mono- and di-C₁-C₆-alkylamides orarylamides, as esters, for example as allyl esters, propargyl esters,C₁-C₁₀-alkyl esters, alkoxyalkyl esters, tefuryl((tetrahydrofuran-2-yl)methyl) esters and also as thioesters, forexample as C₁-C₁₀-alkylthio esters. Preferred mono- anddi-C₁-C₆-alkylamides are the methyl and the dimethylamides. Preferredarylamides are, for example, the anilides and the 2-chloroaniides.Preferred alkyl esters are, for example, the methyl, ethyl, propyl,isopropyl, butyl, isobutyl, pentyl, mexyl (1-methylhexyl), meptyl(1-methylheptyl), heptyl, octyl or isooctyl (2-ethylhexyl) esters.Preferred C₁-C₄-alkoxy-C₁-C₄-alkyl esters are the straight-chain orbranched C₁-C₄-alkoxy ethyl esters, for example the 2-methoxyethyl,2-ethoxyethyl, 2-butoxyethyl (butotyl), 2-butoxypropyl or 3-butoxypropylester. An example of a straight-chain or branched C₁-C₁₀-alkylthio esteris the ethylthio ester.

The organic moieties mentioned in the definition of the variables R¹ toR¹⁴ and R^(a) to R^(e), are—like the term halogen—collective terms forindividual enumerations of the individual group members. The termhalogen denotes in each case fluorine, chlorine, bromine or iodine. Allhydrocarbon chains, e.g. all alkyl, alkenyl, alkynyl, alkoxy chains, canbe straight-chain or branched, the prefix C_(n)-C_(m) denoting in eachcase the possible number of carbon atoms in the group.

Examples of such meanings are:

-   -   C₁-C₃-alkyl and also the C₁-C₃-alkyl moieties of        di(C₁-C₃-alkyl)amino, C₁-C₃-alkoxy-C₁-C₃-alkyl: for example CH₃,        C₂H₅, n-propyl and CH(CH₃)₂;    -   C₁-C₄-alkyl and also the C₁-C₄-alkyl moieties of        phenyl-C₁-C₄-alkyl: for example CH₃, C₂H₅, n-propyl, CH(CH₃)₂,        n-butyl, CH(CH₃)—C₂H₅, CH₂—CH(CH₃)₂ and C(CH₃)₃;    -   C₁-C₆-alkyl and also the C₁-C₆-alkyl moieties of        C₁-C₆-cyanoalkyl, C₁-C₆-alkyoxy-C₁-C₆-alkyl,        C₁-C₆-alkoxy-C₁-C₆-alkoxy-C₁-C₆-alkyl,        di(C₁-C₆-alkoxy)C₁-C₆-alkyl, C₁-C₆-haloalkoxy-C₁-C₆-alkyl,        C₃-C₆-alkenyloxy-C₁-C₆-alkyl, C₃-C₆-haloalkenyloxy-C₁-C₆-alkyl,        C₃-C₆-alkenyloxy-C₁-C₆-alkoxy-C₁-C₆-alkyl,        C₁-C₆-alkylthio-C₁-C₆-alkyl, C₁-C₆-alkylsulfinyl-C₁-C₆-alkyl,        C₁-C₆-alkylsulfonyl-C₁-C₆-alkyl,        C₁-C₆-alkylcarbonyl-C₁-C₆-alkyl,        C₁-C₆-alkoxycarbonyl-C₁-C₆-alkyl,        C₁-C₆-haloalkoxycarbonyl-C₁-C₆-alkyl,        C₃-C₆-alkenyloxycarbonyl-C₁-C₆-alkyl,        C₃-C₆-alkynyloxycarbonyl-C₁-C₆-alkyl,        (C₁-C₆-alkylcarbonyl)amino, amino-C₁-C₆-alkyl,        (C₁-C₆-alkyl)amino-C₁-C₆-alkyl,        di(C₁-C₆-alkyl)amino-C₁-C₆-alkyl, aminocarbonyl-C₁-C₆-alkyl,        (C₁-C₆-alkyl)aminocarbonyl-C₁-C₆-alkyl,        di(C₁-C₆-alkyl)aminocarbonyl-C₁-C₆-alkyl,        C₃-C₆-cycloalkyl-C₁-C₆-alkyl, C₃-C₆-heterocyclyl-C₁-C₆-alkyl:        C₁-C₄-alkyl as mentioned above, and also, for example, n-pentyl,        1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl,        1-ethylpropyl, n-hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl,        1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl,        1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl,        2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl,        1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl,        1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl or        1-ethyl-2-methylpropyl, preferably methyl, ethyl, n-propyl,        1-methylethyl, n-butyl, 1,1-dimethylethyl, n-pentyl or n-hexyl;    -   C₁-C₃-haloalkyl: C₁-C₃-alkyl as mentioned above which is        partially or fully substituted by fluorine, chlorine, bromine        and/or iodine, for example, chloromethyl, dichloromethyl,        trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl,        chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl,        bromomethyl, iodomethyl, 2-fluoroethyl, 2-chloroethyl,        2-bromoethyl, 2-iodoethyl, 2,2-difluoroethyl,        2,2,2-trifluoroethyl, 2-chloro-2-fluoroethyl,        2-chloro-2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl,        2,2,2-trichloroethyl, pentafluoroethyl, 2-fluoropropyl,        3-fluoropropyl, 2,2-difluoropropyl, 2,3-difluoropropyl,        2-chloropropyl, 3-chloropropyl, 2,3-dichloropropyl,        2-bromopropyl, 3-bromopropyl, 3,3,3-trifluoropropyl,        3,3,3-trichloropropyl, 2,2,3,3,3-pentafluoropropyl,        heptafluoropropyl, 1-(fluoromethyl)-2-fluoroethyl,        1-(chloromethyl)-2-chloroethyl, 1-(bromomethyl)-2-bromoethyl;    -   C₁-C₄-haloalkyl: C₁-C₄-alkyl as mentioned above which is        partially or fully substituted by fluorine, chlorine, bromine        and/or iodine, for example, chloromethyl, dichloromethyl,        trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl,        chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl,        bromomethyl, iodomethyl, 2-fluoroethyl, 2-chloroethyl,        2-bromoethyl, 2-iodoethyl, 2,2-difluoroethyl,        2,2,2-trifluoroethyl, 2-chloro-2-fluoroethyl,        2-chloro-2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl,        2,2,2-trichloroethyl, pentafluoroethyl, 2-fluoropropyl,        3-fluoropropyl, 2,2-difluoropropyl, 2,3-difluoropropyl,        2-chloropropyl, 3-chloropropyl, 2,3-dichloropropyl,        2-bromopropyl, 3-bromopropyl, 3,3,3-trifluoropropyl,        3,3,3-trichloropropyl, 2,2,3,3,3-pentafluoropropyl,        heptafluoropropyl, 1-(fluoromethyl)-2-fluoroethyl,        1-(chloromethyl)-2-chloroethyl, 1-(bromomethyl)-2-bromoethyl,        4-fluorobutyl, 4-chlorobutyl, 4-bromobutyl, nonafluorobutyl,        1,1,2,2,-tetrafluoroethyl and        1-trifluoromethyl-1,2,2,2-tetrafluoroethyl;    -   C₁-C₆-haloalkyl: C₁-C₄-haloalkyl as mentioned above, and also,        for example, 5-fluoropentyl, 5-chloropentyl, 5-bromopentyl,        5-iodopentyl, undecafluoropentyl, 6-fluorohexyl, 6-chlorohexyl,        6-bromohexyl, 6-iodohexyl and dodecafluorohexyl;    -   C₃-C₆-alkenyl and also the C₃-C₆-alkenyl moieties of        C₃-C₆-alkenyloxy-C₁-C₆-alkyl,        C₃-C₆-alkenyloxy-C₁-C₆-alkoxy-C₁-C₆-alkyl,        C₃-C₆-alkenyloxycarbonyl-C₁-C₆-alkyl: for example 1-propenyl,        2-propenyl, 1-methylethenyl, 1-butenyl, 2-butenyl, 3-butenyl,        1-methyl-1-propenyl, 2-methyl-1-propenyl, 1-methyl-2-propenyl,        2-methyl-2-propenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl,        4-pentenyl, 1-methyl-1-butenyl, 2-methyl-1-butenyl,        3-methyl-1-butenyl, 1-methyl-2-butenyl, 2-methyl-2-butenyl,        3-methyl-2-butenyl, 1-methyl-3-butenyl, 2-methyl-3-butenyl,        3-methyl-3-butenyl, 1,1-dimethyl-2-propenyl,        1,2-dimethyl-1-propenyl, 1,2-dimethyl-2-propenyl,        1-ethyl-1-propenyl, 1-ethyl-2-propenyl, 1-hexenyl, 2-hexenyl,        3-hexenyl, 4-hexenyl, 5-hexenyl, 1-methyl-1-pentenyl,        2-methyl-1-pentenyl, 3-methyl-1-pentenyl, 4-methyl-1-pentenyl,        1-methyl-2-pentenyl, 2-methyl-2-pentenyl, 3-methyl-2-pentenyl,        4-methyl-2-pentenyl, 1-methyl-3-pentenyl, 2-methyl-3-pentenyl,        3-methyl-3-pentenyl, 4-methyl-3-pentenyl, 1-methyl-4-pentenyl,        2-methyl-4-pentenyl, 3-methyl-4-pentenyl, 4-methyl-4-pentenyl,        1,1-dimethyl-2-butenyl, 1,1-dimethyl-3-butenyl,        1,2-dimethyl-1-butenyl, 1,2-dimethyl-2-butenyl,        1,2-dimethyl-3-butenyl, 1,3-dimethyl-1-butenyl,        1,3-dimethyl-2-butenyl, 1,3-dimethyl-3-butenyl,        2,2-dimethyl-3-butenyl, 2,3-dimethyl-1-butenyl,        2,3-dimethyl-2-butenyl, 2,3-dimethyl-3-butenyl,        3,3-dimethyl-1-butenyl, 3,3-dimethyl-2-butenyl,        1-ethyl-1-butenyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl,        2-ethyl-1-butenyl, 2-ethyl-2-butenyl, 2-ethyl-3-butenyl,        1,1,2-trimethyl-2-propenyl, 1-ethyl-1-methyl-2-propenyl,        1-ethyl-2-methyl-1-propenyl and 1-ethyl-2-methyl-2-propenyl;    -   C₃-C₆-haloalkenyl and also the C₃-C₆-haloalkenyl moieties of        C₃-C₆-haloalkenyloxy-C₁-C₆-alkyl: a C₃-C₆-alkenyl radical as        mentioned above which is partially or fully substituted by        fluorine, chlorine, bromine and/or iodine, for example        2-chloroprop-2-en-1-yl, 3-chloroprop-2-en-1-yl,        2,3-dichloroprop-2-en-1-yl, 3,3-dichloroprop-2-en-1-yl,        2,3,3-trichloro-2-en-1-yl, 2,3-dichlorobut-2-en-1-yl,        2-bromoprop-2-en-1-yl, 3-bromoprop-2-en-1-yl,        2,3-dibromoprop-2-en-1-yl, 3,3-dibromoprop-2-en-1-yl,        2,3,3-tribromo-2-en-1-yl or 2,3-dibromobut-2-en-1-yl;    -   C₃-C₆-alkynyl and also the C₃-C₆-alkynyl moieties of        C₃-C₆-alkynyloxycarbonyl-C₁-C₆-alkyl: for example 1-propynyl,        2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl,        1-methyl-2-propynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl,        4-pentynyl, 1-methyl-2-butynyl, 1-methyl-3-butynyl,        2-methyl-3-butynyl, 3-methyl-1-butynyl, 1,1-dimethyl-2-propynyl,        1-ethyl-2-propynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl,        5-hexynyl, 1-methyl-2-pentynyl, 1-methyl-3-pentynyl,        1-methyl-4-pentynyl, 2-methyl-3-pentynyl, 2-methyl-4-pentynyl,        3-methyl-1-pentynyl, 3-methyl-4-pentynyl, 4-methyl-1-pentynyl,        4-methyl-2-pentynyl, 1,1-dimethyl-2-butynyl,        1,1-dimethyl-3-butynyl, 1,2-dimethyl-3-butynyl,        2,2-dimethyl-3-butynyl, 3,3-dimethyl-1-butynyl,        1-ethyl-2-butynyl, 1-ethyl-3-butynyl, 2-ethyl-3-butynyl and        1-ethyl-1-methyl-2-propynyl;    -   C₃-C₆-haloalkynyl: a C₃-C₆-alkynyl radical as mentioned above        which is partially or fully substituted by fluorine, chlorine,        bromine and/or iodine, for example 1,1-difluoroprop-2-yn-1-yl,        3-chloroprop-2-yn-1-yl, 3-bromoprop-2-yn-1-yl,        3-iodoprop-2-yn-1-yl, 4-fluorobut-2-yn-1-yl,        4-chlorobut-2-yn-1-yl, 1,1-difluorobut-2-yn-1-yl,        4-iodobut-3-yn-1-yl, 5-fluoropent-3-yn-1-yl,        5-iodopent-4-yn-1-yl, 6-fluorohex-4-yn-1-yl or        6-iodohex-5-yn-1-yl;    -   C₁-C₃-alkoxy and also the C₁-C₃-alkoxy moieties of        C₁-C₃-alkoxy-C₁-C₃-alkyl, C₁-C₃-alkoxycarbonyl: for example        methoxy, ethoxy, propoxy;    -   C₁-C₄-alkoxy and also the C₁-C₄-alkoxy moieties of        C₁-C₄-alkoxycarbonyl: for example methoxy, ethoxy, propoxy,        1-methylethoxy butoxy, 1-methylpropoxy, 2-methylpropoxy and        1,1-dimethylethoxy;    -   C₁-C₆-alkoxy and also the C₁-C₆-alkoxy moieties of        C₁-C₆-alkyoxy-C₁-C₆-alkyl,        C₁-C₆-alkoxy-C₁-C₆-alkoxy-C₁-C₆-alkyl,        di(C₁-C₆-alkoxy)C₁-C₆-alkyl,        C₃-C₆-alkenyloxy-C₁-C₆-alkoxy-C₁-C₆-alkyl,        C₁-C₆-alkoxycarbonyl-C₁-C₆-alkyl: C₁-C₄-alkoxy as mentioned        above, and also, for example, pentoxy, 1-methylbutoxy,        2-methylbutoxy, 3-methoxylbutoxy, 1,1-dimethylpropoxy,        1,2-dimethylpropoxy, 2,2-dimethylpropoxy, 1-ethylpropoxy,        hexoxy, 1-methylpentoxy, 2-methylpentoxy, 3-methylpentoxy,        4-methylpentoxy, 1,1-dimethylbutoxy, 1,2-dimethylbutoxy,        1,3-dimethylbutoxy, 2,2-dimethylbutoxy, 2,3-dimethylbutoxy,        3,3-dimethylbutoxy, 1-ethylbutoxy, 2-ethylbutoxy,        1,1,2-trimethylpropoxy, 1,2,2-trimethylpropoxy,        1-ethyl-1-methylpropoxy and 1-ethyl-2-methylpropoxy.    -   C₁-C₃-haloalkoxy: a C₁-C₃-alkoxy radical as mentioned above        which is partially or fully substituted by fluorine, chlorine,        bromine and/or iodine, i.e., for example, fluoromethoxy,        difluoromethoxy, trifluoromethoxy, chlorodifluoromethoxy,        bromodifluoromethoxy, 2-fluoroethoxy, 2-chloroethoxy,        2-bromomethoxy, 2-iodoethoxy, 2,2-difluoroethoxy,        2,2,2-trifluoroethoxy, 2-chloro-2-fluoroethoxy,        2-chloro-2,2-difluoroethoxy, 2,2-dichloro-2-fluoroethoxy,        2,2,2-trichloroethoxy, pentafluoroethoxy, 2-fluoropropoxy,        3-fluoropropoxy, 2-chloropropoxy, 3-chloropropoxy,        2-bromopropoxy, 3-bromopropoxy, 2,2-difluoropropoxy,        2,3-difluoropropoxy, 2,3-dichloropropoxy,        3,3,3-trifluoropropoxy, 3,3,3-trichloropropoxy,        2,2,3,3,3-pentafluoropropoxy, heptafluoropropoxy,        1-(fluoromethyl)-2-fluoroethoxy,        1-(chloromethyl)-2-chloroethoxy, 1-(bromo-methyl)-2-bromoethoxy;    -   C₁-C₄-haloalkoxy: a C₁-C₄-alkoxy radical as mentioned above        which is partially or fully substituted by fluorine, chlorine,        bromine and/or iodine, i.e., for example, fluoromethoxy,        difluoromethoxy, trifluoromethoxy, chlorodifluoromethoxy,        bromodifluoromethoxy, 2-fluoroethoxy, 2-chloroethoxy,        2-bromomethoxy, 2-iodoethoxy, 2,2-difluoroethoxy,        2,2,2-trifluoroethoxy, 2-chloro-2-fluoroethoxy,        2-chloro-2,2-difluoroethoxy, 2,2-dichloro-2-fluoroethoxy,        2,2,2-trichloroethoxy, pentafluoroethoxy, 2-fluoropropoxy,        3-fluoropropoxy, 2-chloropropoxy, 3-chloropropoxy,        2-bromopropoxy, 3-bromopropoxy, 2,2-difluoropropoxy,        2,3-difluoropropoxy, 2,3-dichloropropoxy,        3,3,3-trifluoropropoxy, 3,3,3-trichloropropoxy,        2,2,3,3,3-pentafluoropropoxy, heptafluoropropoxy,        1-(fluoromethyl)-2-fluoroethoxy,        1-(chloromethyl)-2-chloroethoxy, 1-(bromo-methyl)-2-bromoethoxy,        4-fluorobutoxy, 4-chlorobutoxy, 4-bromobutoxy and        nonafluorobutoxy;    -   C₁-C₆-haloalkoxy and also the C₁-C₆-haloalkoxy moieties of        C₁-C₆-haloalkoxy-C₁-C₆-alkyl,        C₁-C₆-haloalkoxycarbonyl-C₁-C₆-alkyl: a C₁-C₄-haloalkoxy as        mentioned above, and also, for example, 5-fluoropentoxy,        5-chloropentoxy, 5-bromopentoxy, 5-iodopentoxy,        undecafluoropentoxy, 6-fluorohexoxy, 6-chlorohexoxy,        6-bromohexoxy, 6-iodohexoxy and dodecafluorohexoxy;    -   C₁-C₃-alkylthio: for example methylthio, ethylthio, propylthio,        1-methylethylthio;    -   C₁-C₄-alkylthio: for example methylthio, ethylthio, propylthio,        1-methylethylthio, butylthio, 1-methylpropylthio,        2-methylpropylthio and 1,1-dimethylethylthio;    -   C₁-C₆-alkylthio and also the C₁-C₆-alkylthio moieties of        C₁-C₆-alkylthio-C₁-C₆-alkyl: C₁-C₄-alkylthio as mentioned above,        and also, for example, pentylthio, 1-methylbutylthio,        2-methylbutylthio, 3-methylbutylthio, 2,2-dimethylpropylthio,        1-ethylpropylthio, hexylthio, 1,1-dimethylpropylthio,        1,2-dimethylpropylthio, 1-methylpentylthio, 2-methylpentylthio,        3-methylpentylthio, 4-methylpentylthio, 1,1-dimethylbutylthio,        1,2-dimethylbutylthio, 1,3-dimethylbutylthio,        2,2-dimethylbutylthio, 2,3-dimethylbutylthio,        3,3-dimethylbutylthio, 1-ethylbutylthio, 2-ethylbutylthio,        1,1,2-trimethylpropylthio, 1,2,2-trimethylpropylthio,        1-ethyl-1-methylpropylthio and 1-ethyl-2-methylpropylthio;    -   C₁-C₆-alkylsulfinyl (C₁-C₆-alkyl-S(═O)-) and also the        C₁-C₆-alkylsulfinyl moieties of C₁-C₆-alkylsulfinyl-C₁-C₆-alkyl:        for example methylsulfinyl, ethylsulfinyl, propylsulfinyl,        1-methylethylsulfinyl, butylsulfinyl, 1-methylpropylsulfinyl,        2-methylpropylsulfinyl, 1,1-di-methylethylsulfinyl,        pentylsulfinyl, 1-methylbutylsulfinyl, 2-methylbutylsulfinyl,        3-methylbutylsulfinyl, 2,2-dimethylpropylsulfinyl,        1-ethylpropylsulfinyl, 1,1-dimethylpropylsulfinyl,        1,2-dimethylpropylsulfinyl, hexylsulfinyl,        1-methylpentylsulfinyl, 2-methylpentylsulfinyl,        3-methylpentylsulfinyl, 4-methylpentyl-sulfinyl,        1,1-dimethylbutylsulfinyl, 1,2-dimethylbutylsulfinyl,        1,3-dimethylbutyl-sulfinyl, 2,2-dimethylbutylsulfinyl,        2,3-dimethylbutylsulfinyl, 3,3-dimethylbutyl-sulfinyl,        1-ethylbutylsulfinyl, 2-ethylbutylsulfinyl,        1,1,2-trimethylpropylsulfinyl, 1,2,2-trimethylpropylsulfinyl,        1-ethyl-1-methylpropylsulfinyl and        1-ethyl-2-methylpropylsulfinyl;    -   C₁-C₆-alkylsulfonyl (C₁-C₆-alkyl-S(O)₂—) and also the        C₁-C₆-alkylsulfonyl moieties of C₁-C₆-alkylsulfonyl-C₁-C₆-alkyl:        for example methylsulfonyl, ethylsulfonyl, propylsulfonyl,        1-methylethylsulfonyl, butylsulfonyl, 1-methylpropylsulfonyl,        2-methyl-propylsulfonyl, 1,1-dimethylethylsulfonyl,        pentylsulfonyl, 1-methylbutylsulfonyl, 2-methylbutylsulfonyl,        3-methylbutylsulfonyl, 1,1-dimethylpropylsulfonyl,        1,2-dimethylpropylsulfonyl, 2,2-dimethylpropylsulfonyl,        1-ethylpropylsulfonyl, hexylsulfonyl, 1-methylpentylsulfonyl,        2-methylpentylsulfonyl, 3-methylpentylsulfonyl,        4-methylpentylsulfonyl, 1,1-dimethylbutylsulfonyl,        1,2-dimethylbutylsulfonyl, 1,3-dimethylbutylsulfonyl,        2,2-dimethylbutylsulfonyl, 2,3-dimethylbutylsulfonyl,        3,3-dimethylbutylsulfonyl, 1-ethylbutylsulfonyl,        2-ethylbutylsulfonyl, 1,1,2-trimethylpropylsulfonyl,        1,2,2-trimethylpropylsulfonyl, 1-ethyl-1-methylpropylsulfonyl        and 1-ethyl-2-methylpropylsulfonyl;    -   (C₁-C₃-alkyl)amino: for example methylamino, ethylamino,        propylamino, 1-methylethyl-amino;    -   (C₁-C₄-alkyl)amino: for example methylamino, ethylamino,        propylamino, 1-methylethyl-amino, butylamino,        1-methylpropylamino, 2-methylpropylamino or        1,1-dimethylethylamino;    -   (C₁-C₆-alkyl)amino: (C₁-C₄-alkylamino) as mentioned above, and        also, for example, pentylamino, 1-methylbutylamino,        2-methylbutylamino, 3-methylbutylamino, 2,2-dimethylpropylamino,        1-ethylpropylamino, hexylamino, 1,1-dimethylpropylamino,        1,2-dimethylpropylamino, 1-methylpentylamino,        2-methylpentylamino, 3-methylpentylamino, 4-methylpentylamino,        1,1-dimethylbutylamino, 1,2-dimethylbutylamino,        1,3-dimethylbutylamino, 2,2-dimethylbutylamino,        2,3-dimethylbutyl-amino 3,3-dimethylbutylamino,        1-ethylbutylamino, 2-ethylbutylamino,        1,1,2-trimethylpropylamino, 1,2,2-trimethyl-propylamino,        1-ethyl-1-methylpropylamino or 1-ethyl-2-methylpropylamino;    -   di(C₁-C₆-alkyl)amino: di(C₁-C₄-alkyl)amino as mentioned above,        and also, for example, N-methyl-N-pentylamino,        N-methyl-N-(1-methylbutyl)amino,        N-methyl-N-(2-methylbutyl)amino,        N-methyl-N-(3-methylbutyl)amino,        N-methyl-N-(2,2-dimethylpropyl)amino,        N-methyl-N-(1-ethylpropyl)amino, N-methyl-N-hexylamino,        N-methyl-N-(1,1-dimethylpropyl)amino,        N-methyl-N-(1,2-dimethylpropyl)amino,        N-methyl-N-(1-methylpentyl)amino,        N-methyl-N-(2-methylpentyl)amino,        N-methyl-N-(3-methylpentyl)amino,        N-methyl-N-(4-methylpentyl)amino,        N-methyl-N-(1,1-dimethylbutyl)amino,        N-methyl-N-(1,2-dimethylbutyl)amino,        N-methyl-N-(1,3-dimethylbutyl)amino,        N-methyl-N-(2,2-dimethylbutyl)amino,        N-methyl-N-(2,3-dimethylbutyl)amino,        N-methyl-N-(3,3-dimethylbutyl)amino,        N-methyl-N-(1-ethylbutyl)amino, N-methyl-N-(2-ethylbutyl)amino,        N-methyl-N-(1,1,2-trimethylpropyl)amino,        N-methyl-N-(1,2,2-trimethylpropyl)amino,        N-methyl-N-(1-ethyl-1-methylpropyl)amino,        N-methyl-N-(1-ethyl-2-methylpropyl)amino, N-ethyl-N-pentylamino,        N-ethyl-N-(1-methylbutyl)amino, N-ethyl-N-(2-methylbutyl)amino,        N-ethyl-N-(3-methylbutyl)amino,        N-ethyl-N-(2,2-dimethylpropyl)amino,        N-ethyl-N-(1-ethylpropyl)amino, N-ethyl-N-hexylamino,        N-ethyl-N-(1,1-dimethylpropyl)amino,        N-ethyl-N-(1,2-dimethylpropyl)amino,        N-ethyl-N-(1-methylpentyl)amino,        N-ethyl-N-(2-methyl-pentyl)amino,        N-ethyl-N-(3-methylpentyl)amino,        N-ethyl-N-(4-methylpentyl)amino,        N-ethyl-N-(1,1-dimethylbutyl)amino,        N-ethyl-N-(1,2-dimethylbutyl)amino,        N-ethyl-N-(1,3-dimethylbutyl)amino,        N-ethyl-N-(2,2-dimethylbutyl)amino,        N-ethyl-N-(2,3-dimethylbutyl)amino,        N-ethyl-N-(3,3-dimethylbutyl)amino,        N-ethyl-N-(1-ethylbutyl)amino, N-ethyl-N-(2-ethylbutyl)amino,        N-ethyl-N-(1,1,2-trimethylpropyl)amino,        N-ethyl-N-(1,2,2-trimethylpropyl)amino,        N-ethyl-N-(1-ethyl-1-methylpropyl)amino,        N-ethyl-N-(1-ethyl-2-methylpropyl)amino, N-propyl-N-pentylamino,        N-butyl-N-pentylamino, N,N-dipentylamino, N-propyl-N-hexylamino,        N-butyl-N-hexylamino, N-pentyl-N-hexylamino or N,N-dihexylamino;    -   C₃-C₆-cycloalkyl and also the cycloalkyl moieties of        C₃-C₆-cycloalkyl-C₁-C₆-alkyl: monocyclic saturated hydrocarbons        having 3 to 6 ring members, such as cyclopropyl, cyclobutyl,        cyclopentyl and cyclohexyl;    -   C₃-C₆-heterocyclyl and also the heterocyclyl moieties of        C₃-C₆-heterocyclyl-C₁-C₆-alkyl: aliphatic heterocycle having 3        to 6 ring members which, in addition to carbon atoms, contains 1        to 4 nitrogen atoms, or 1 to 3 nitrogen atoms and an oxygen or        sulphur atom, or an oxygen or a sulphur atom, for example

three- or four-membered heterocycles like 2-oxetanyl, 3-oxetanyl,2-thietanyl, 3-thietanyl, 1-azetidinyl, 2-azetidinyl, 1-azetinyl,2-azetinyl; five-membered saturated heterocycles like2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahydrothienyl,3-tetrahydrothienyl, 1-pyrrolidinyl, 2-pyrrolidinyl, 3-pyrrolidinyl,3-isoxazolidinyl, 4-isoxazolidinyl, 5-isoxazolidinyl,2-isothiazolidinyl, 3-isothiazolidinyl, 4-isothiazolidinyl,5-isothiazolidinyl, 1-pyrazolidinyl, 3-pyrazolidinyl, 4-pyrazolidinyl,5-pyrazolidinyl, 2-oxazolidinyl, 4-oxazolidinyl, 5-oxazolidinyl,2-thiazolidinyl, 4-thiazolidinyl, 5-thiazolidinyl, 1-imidazolidinyl,2-imidazolidinyl, 4-imidazolidinyl, 3-oxazolidinyl,1,2,4-oxadiazolidin-3-yl, 1,2,4-oxadiazolidin-5-yl, 3-thiazolidinyl,1,2,4-thiadiazolidin-3-yl, 1,2,4-thiadiazolidin-5-yl,1,2,4-triazolidin-3-yl, 1,2,4-oxadiazolidin-2-yl,1,2,4-oxadiazolidin-4-yl, 1,3,4-oxadiazolidin-2-yl,1,2,4-thiadiazolidin-2-yl, 1,2,4-thiadiazolidin-4-yl,1,3,4-thiadiazolidin-2-yl, 1,2,4-triazolidin-1-yl,1,3,4-triazolidin-2-yl; six-membered saturated heterocycles like1-piperidinyl, 2-piperidinyl, 3-piperidinyl, 4-piperidinyl,1,3-dioxan-5-yl, 1,4-dioxanyl, 1,3-dithian-5-yl, 1,3-dithianyl,1,3-oxathian-5-yl, 1,4-oxathianyl, 2-tetrahydropyranyl,3-tetrahydopyranyl, 4-tetrahydropyranyl, 2-tetrahydrothiopyranyl,3-tetrahydrothiopyranyl, 4-tetrahydrothiopyranyl,1-hexahydropyridazinyl, 3-hexahydropyridazinyl, 4-hexahydropyridazinyl,1-hexahydropyrimidinyl, 2-hexahydropyrimidinyl, 4-hexahydropyrimidinyl,5-hexahydropyrimidinyl, 1-piperazinyl, 2-piperazinyl,1,3,5-hexahydrotriazin-1-yl, 1,3,5-hexahydrotriazin-2-yl,1,2,4-hexahydrotriazin-1-yl, 1,2,4-hexahydrotriazin-3-yl,tetrahydro-1,3-oxazin-1-yl, tetrahydro-1,3-oxazin-2-yl,tetrahydro-1,3-oxazin-6-yl, 1-morpholinyl, 2-morpholinyl, 3-morpholinyl;

-   -   5- or 6 membered heteroaryl: aromatic heteroaryl having 5 or 6        ring members which, in addition to carbon atoms, contains 1 to 4        nitrogen atoms, or 1 to 3 nitrogen atoms and an oxygen or        sulphur atom, or an oxygen or a sulphur atom, for example        5-membered aromatic rings like furyl (for example 2-furyl,        3-furyl), thienyl (for example 2-thienyl, 3-thienyl), pyrrolyl        (for example pyrrol-2-yl, pyrrol-3-yl), pyrazolyl (for example        pyrazol-3-yl, pyrazol-4-yl), isoxazolyl (for example        isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl), isothiazolyl (for        example isothiazol-3-yl, isothiazol-4-yl, isothiazol-5-yl),        imidazolyl (for example imidazole-2-yl, imidazole-4-yl),        oxazolyl (for example oxazol-2-yl, oxazol-4-yl, oxazol-5-yl),        thiazolyl (for example thiazol-2-yl, thiazol-4-yl,        thiazol-5-yl), oxadiazolyl (for example 1,2,3-oxadiazol-4-yl,        1,2,3-oxadiazol-5-yl, 1,2,4-oxadiazol-3-yl,        1,2,4-oxadiazol-5-yl, 1,3,4-oxadiazol-2-yl), thiadiazolyl (for        example 1,2,3-thiadiazol-4-yl, 1,2,3-thiadiazol-5-yl,        1,2,4-thiadiazol-3-yl, 1,2,4-thiadiazol-5-yl,        1,3,4-thiadiazolyl-2-yl), triazolyl (for example        1,2,3-triazol-4-yl, 1,2,4-triazol-3-yl); 1-tetrazolyl;        6-membered aromatic rings like pyridyl (for example        pyridine-2-yl, pyridine-3-yl, pyridine-4-yl), pyrazinyl (for        example pyridazin-3-yl, pyridazin-4-yl), pyrimidinyl (for        example pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl),        pyrazin-2-yl, triazinyl (for example 1,3,5-triazin-2-yl,        1,2,4-triazin-3-yl, 1,2,4-triazin-5-yl, 1,2,4-triazin-6-yl);    -   3- to 7-membered carbocyclus: a three- to seven-membered        monocyclic, saturated, partial unsaturated or aromatic cycle        having three to seven ring members which comprises apart from        carbon atoms optionally one or two ring members selected from        the group consisting of —N(R¹²)—, —N═N—, —C(═O)—, —O— and —S—.

The preferred embodiments of the invention mentioned herein below haveto be understood as being preferred either independently from each otheror in combination with one another.

According to a preferred embodiment of the invention preference is alsogiven to those uracilpyridines of formula (I), wherein the variables,either independently of one another or in combination with one another,have the following meanings:

Preferred are the uracilpyridines of formula (I) wherein

-   -   R¹ is hydrogen, NH₂ or C₁-C₆-alkyl;        -   preferably is NH₂ or C₁-C₄-alkyl;        -   particularly preferred is NH₂ or CH₃;        -   also preferably is C₁-C₆-alkyl;        -   particularly preferred is C₁-C₄-alkyl;        -   especially preferred is CH₃.

Also preferred are the uracilpyridines of formula (I) wherein

-   -   R² is C₁-C₆-alkyl or C₁-C₆-haloalkyl;        -   preferably is C₁-C₄-alkyl or C₁-C₄-haloalkyl;        -   more preferred is C₁-C₄-haloalkyl;        -   particularly preferred is C₁-C₂-haloalkyl;        -   especially preferred is CF₃.

Also preferred are the uracilpyridines of formula (I) wherein

-   -   R³ is H;        -   also preferably is C₁-C₆-alkyl,        -   particularly preferred is C₁-C₄-alkyl,        -   especially preferred is CH₃.

Also preferred are the uracilpyridines of formula (I) wherein

-   -   R⁴ is H, F or Cl;        -   particularly preferred is H or F;        -   especially preferred is H;        -   also particularly preferred is H or Cl;        -   especially preferred is Cl;        -   also particularly preferred is F or Cl;        -   especially preferred is F.

Also preferred are the uracilpyridines of formula (I) wherein

-   -   R⁵ is halogen or CN;        -   preferably F, Cl, Br or CN;        -   particularly preferred is F, Cl or CN;        -   especially preferred is Cl or CN;        -   more preferred is Cl;        -   also more preferred is CN;        -   also especially preferred is F or Cl;        -   more preferred is F.

Also preferred are the uracilpyridines of formula (I) wherein

-   -   R⁶ is H, C₁-C₃-alkyl, C₁-C₃-haloalkyl, C₁-C₃-alkoxy,        C₁-C₃-haloalkoxy or C₁-C₃-alkylthio;        -   particularly preferred is H, C₁-C₃-alkyl, C₁-C₃-haloalkyl or            C₁-C₃-alkoxy;        -   especially preferred is H, C₁-C₃-alkyl or C₁-C₃-alkoxy;        -   more preferred is H, CH₃ or OCH₃.

Also preferred are the uracilpyridines of formula (I) wherein

-   -   R⁷ is H, halogen or C₁-C₃-alkyl;        -   particularly preferred is H, F or CH₃;        -   especially preferred is H.

Also preferred are the uracilpyridines of formula (I) wherein

-   -   R⁸ is OR⁹, SR⁹, NR¹⁰R¹¹, NR⁹S(O)₂R¹⁰ or NR⁹S(O)₂NR¹⁰R¹¹;        -   particularly preferred is OR⁹, NR¹⁰R¹¹, NR⁹S(O)₂R¹⁰ or            NR⁹S(O)₂NR¹⁰R¹¹;        -   especially preferred OR⁹, NR⁹S(O)₂R¹⁰ or NR⁹S(O)₂NR¹⁰R¹¹;        -   especially preferred is OR⁹ or NR⁹S(O)₂R¹⁰.

Also preferred are the uracilpyridines of formula (I) wherein

-   -   R⁹ is hydrogen, C₁-C₆-alkyl, C₃-C₆-alkenyl, C₃-C₆-alkynyl,        C₁-C₆-haloalkyl, C₃-C₆-haloalkenyl, C₃-C₆-haloalkynyl,        C₁-C₆-cyanoalkyl, C₁-C₆-alkoxy-C₁-C₆-alkyl,        C₁-C₆-alkoxy-C₁-C₆-alkoxy-C₁-C₆-alkyl,        di(C₁-C₆-alkoxy)C₁-C₆-alkyl, C₁-C₆-haloalkoxy-C₁-C₆-alkyl,        C₃-C₆-alkenyloxy-C₁-C₆-alkyl, C₃-C₆-haloalkenyloxy-C₁-C₆-alkyl,        C₃-C₆-alkenyloxy-C₁-C₆-alkoxy-C₁-C₆-alkyl,        C₁-C₆-alkylthio-C₁-C₆-alkyl, C₁-C₆-alkylsulfinyl-C₁-C₆-alkyl,        C₁-C₆-alkylsulfonyl-C₁-C₆-alkyl,        C₁-C₆-alkylcarbonyl-C₁-C₆-alkyl,        C₁-C₆-alkoxycarbonyl-C₁-C₆-alkyl,        C₁-C₆-haloalkoxy-carbonyl-C₁-C₆-alkyl,        C₃-C₆-alkenyloxycarbonyl-C₁-C₆-alkyl,        C₃-C₆-alkynyloxycarbonyl-C₁-C₆-alkyl, amino,(C₁-C₆-alkyl)amino,        di(C₁-C₆-alkyl)amino,(C₁-C₆-alkylcarbonyl)amino,        amino-C₁-C₆-alkyl,(C₁-C₆-alkyl)amino-C₁-C₆-alkyl,        di(C₁-C₆-alkyl)amino-C₁-C₆-alkyl,        aminocarbonyl-C₁-C₆-alkyl,(C₁-C₆-alkyl)aminocarbonyl-C₁-C₆-alkyl,        di(C₁-C₆-alkyl)aminocarbonyl-C₁-C₆-alkyl,        -   N═CR¹²R¹³            -   wherein R¹² and R¹³ independently of one another are H,                C₁-C₄-alkyl or phenyl; C₃-C₆-cycloalkyl,                C₃-C₆-cycloalkyl-C₁-C₆-alkyl, C₃-C₆-heterocyclyl,                phenyl, phenyl-C₁-C₄-alkyl or a 5- or 6 membered                heteroaryl,            -   wherein each cycloalkyl, heterocyclyl, phenyl or                heteroaryl ring can be substituted                -   by one to four substituents selected from R¹⁴ or a                    3- to 7-membered carbocyclus, which carbocyclus                    optionally has in addition to carbon atoms one or                    two ring members selected from the group consisting                    of —N(R¹²)—, —N═N—, —C(═O)—, —O— and —S—, and                -   which carbocyclus is optionally substituted with one                    to four substituents selected from R¹⁴                -    wherein R¹⁴ is halogen, NO₂, CN, C₁-C₄-alkyl,                    C₁-C₄-haloalkyl, C₁-C₄-alkoxy or                    C₁-C₄-alkoxycarbonyl;        -   preferably is hydrogen, C₁-C₆-alkyl, C₃-C₆-alkenyl,            C₃-C₆-alkynyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy-C₁-C₆-alkyl,            di(C₁-C₆-alkoxy)C₁-C₆-alkyl,            C₁-C₆-alkylcarbonyl-C₁-C₆-alkyl,            C₁-C₆-alkoxycarbonyl-C₁-C₆-alkyl or            C₃-C₆-cycloalkyl-C₁-C₆-alkyl;        -   particularly preferred is hydrogen, C₁-C₆-alkyl,            C₃-C₆-alkenyl, C₃-C₆-alkynyl or C₁-C₆-haloalkyl;        -   also particularly preferred is hydrogen, C₁-C₆-alkyl,            C₃-C₆-alkenyl or C₃-C₆-alkynyl;        -   especially preferred is hydrogen, C₁-C₆-alkyl, or            C₃-C₆-alkynyl;        -   more preferred is hydrogen, CH₃, C₂H₅, CH₂CH═CH₂ or CH₂C═CH;        -   most preferred is hydrogen, CH₃, C₂H₅ or CH₂C═CH.

Also preferred are the uracilpyridines of formula (I) wherein

-   -   R¹⁰ is H, C₁-C₆-alkyl or C₃-C₆-cycloalkyl;        -   particularly preferred is H or C₁-C₆-alkyl;        -   more preferred is H;        -   also more preferred is C₁-C₆-alkyl.

Also preferred are the uracilpyridines of formula (I) wherein

-   -   R¹¹ is H, C₁-C₆-alkyl or C₁-C₆-alkoxycarbonyl-C₁-C₆-alkyl;        -   particularly preferred is H or C₁-C₆-alkyl;        -   more preferred is H;        -   also more preferred is C₁-C₆-alkyl.

Also preferred are the uracilpyridines of formula (I) wherein

-   -   R¹² is phenyl or C₁-C₄-alkyl;        -   particularly preferred is phenyl or CH₃;        -   also particularly preferred is phenyl;        -   also particularly preferred is C₁-C₄-alkyl.

Also preferred are the uracilpyridines of formula (I) wherein

-   -   R¹³ is phenyl or C₁-C₄-alkyl;        -   particularly preferred is phenyl or CH₃;        -   also particularly preferred is phenyl;        -   also particularly preferred is C₁-C₄-alkyl.

Also preferred are the uracilpyridines of formula (I) wherein

-   -   R¹⁴ is halogen or C₁-C₆-alkyl;        -   particularly preferred is F, Cl or CH₃;        -   also particularly preferred is halogen;        -   especially preferred is F or C₁;        -   also particularly preferred is C₁-C₆-alkyl;        -   especially preferred is CH₃.

Also preferred are the uracilpyridines of formula (I) wherein

-   -   n is 1 or 2;        -   particularly preferred is 2;        -   also particularly preferred is 1.

Also preferred are the uracilpyridines of formula (I) wherein

-   -   Q is O, S, SO, SO₂, NH or (C₁-C₃-alkyl)N;        -   preferably is O or S;        -   particularly preferred is O.

Also preferred are the uracilpyridines of formula (I) wherein

-   -   W is O,        -   also preferably is S.

Also preferred are the uracilpyridines of formula (I) wherein

-   -   X is O,        -   also preferably is S.

Also preferred are the uracilpyridines of formula (I) wherein

-   -   Y is O,        -   also preferably is S.

Also preferred are the uracilpyridines of formula (I) wherein

-   -   Z is phenyl or pyridyl,        -   each of which is optionally substituted by 1 to 4            substituents selected from the group consisting of halogen,            CN, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy and            C₁-C₆-haloalkoxy;    -    preferably is phenyl,        -   which is optionally substituted by 1 to 4 substituents            selected from the group consisting of halogen, CN,            C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy and            C₁-C₆-haloalkoxy;    -    also preferably is pyridyl,        -   which is optionally substituted by 1 to 4 substituents            selected from the group consisting of halogen, CN,            C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy and            C₁-C₆-haloalkoxy.

Also preferred are the uracilpyridines of formula (I) wherein

-   -   Z is phenyl or pyridyl,        -   each of which is optionally substituted by 1 to 4            substituents selected from the group consisting of halogen,            CN, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy and            C₁-C₆-haloalkoxy;    -    preferably is phenyl or pyridyl,        -   each of which is optionally substituted by 1 to 4            substituents selected from the group consisting of halogen,            C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy or            C₁-C₆-haloalkoxy;    -    particularly preferred is phenyl or pyridyl,        -   each of which is optionally substituted by 1 to 4            substituents selected from the group consisting of halogen            or C₁-C₆-alkyl;    -    especially preferred is phenyl or pyridyl,        -   each of which is optionally substituted by 1 to 4            substituents selected from the group consisting of F, Cl or            CH₃;    -    more preferred is phenyl or pyridyl,        -   each of which is unsubstituted.

Also preferred are the uracilpyridines of formula (I) wherein

-   -   Z is phenyl,        -   which is optionally substituted by 1 to 4 substituents            selected from the group consisting of halogen, CN,            C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy and            C₁-C₆-haloalkoxy;    -    preferably is phenyl,        -   which is optionally substituted by 1 to 4 substituents            selected from the group consisting of halogen, C₁-C₆-alkyl,            C₁-C₆-haloalkyl, C₁-C₆-alkoxy or C₁-C₆-haloalkoxy;    -    particularly preferred is phenyl,        -   which is optionally substituted by 1 to 4 substituents            selected from the group consisting of halogen or            C₁-C₆-alkyl;    -    especially preferred is phenyl        -   which is optionally substituted by 1 to 4 substituents            selected from the group consisting of F, C₁ or CH₃;    -    more preferred is unsubstituted phenyl.

Also preferred are the uracilpyridines of formula (I) wherein

-   -   Z is pyridyl,        -   which is optionally substituted by 1 to 3 substituents            selected from the group consisting of halogen, CN,            C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy and            C₁-C₆-haloalkoxy;    -    preferably is pyridyl,        -   which is optionally substituted by 1 to 3 substituents            selected from the group consisting of halogen, C₁-C₆-alkyl,            C₁-C₆-haloalkyl, C₁-C₆-alkoxy or C₁-C₆-haloalkoxy;    -    particularly preferred is pyridyl,        -   which is optionally substituted by 1 to 3 substituents            selected from the group consisting of halogen or            C₁-C₆-alkyl;    -    especially preferred is pyridyl,        -   which is optionally substituted by 1 to 3 substituents            selected from the group consisting of F, C₁ or CH₃;    -    more preferred is unsubstituted pyridyl.

Also preferred are the uracilpyridines of formula (I) wherein

-   -   Z is selected from the group consisting of Z¹ to Z²⁹

-   -   -   wherein        -   * denotes the point of attachment of Z to X;        -   ** denotes the point of attachment of Z to Q; and        -   R^(a), R^(b), R^(c), R^(d) and R^(e) independently of one            another are            -   H, halogen, CN, C₁-C₆-alkyl, C₁-C₆-haloalkyl,                C₁-C₆-alkoxy, C₁-C₆-haloalkoxy;            -   preferably H, halogen, C₁-C₆-alkyl, C₁-C₆-haloalkyl,                C₁-C₆-alkoxy or C₁-C₆-haloalkoxy;            -   particularly preferred H, halogen or C₁-C₆-alkyl;            -   especially preferred H, F, C, or CH₃;            -   more preferred H.

Also preferred are the uracilpyridines of formula (I) wherein

-   -   Z is selected from the group consisting of Z¹, Z², Z³, Z⁴, Z⁵,        Z⁶, Z⁷, Z⁸, Z⁹, Z¹, Z¹¹, Z¹², Z¹³ and Z²¹ as defined above;        -   particularly preferred is selected from the group consisting            of Z¹, Z², Z⁴, Z⁵, Z⁶, Z⁷, Z⁸, Z⁹, Z¹⁰, Z¹¹ and Z²¹ as            defined above;        -   more particularly preferred is selected from the group            consisting of Z¹, Z⁴, Z⁵, Z⁶, Z⁷ and Z²¹ as defined above;        -   especially preferred is selected from the group consisting            of Z¹, Z⁴, Z⁵, Z⁶ and Z⁷ as defined above;        -   more preferred is selected from the group consisting of Z¹            and Z⁷ as defined above.

Also preferred are the uracilpyridines of formula (I) wherein

-   -   Z is selected from the group consisting of Z¹, Z², Z³, Z⁴, Z⁵,        Z⁶, Z⁷, Z⁸, Z⁹, Z¹⁰, Z¹¹, Z¹², Z¹³ and Z²¹ as defined above;        wherein        -   R^(a), R^(b), R^(c), R^(d) and Re independently of one            another are            -   H, halogen, CN, C₁-C₆-alkyl, C₁-C₆-haloalkyl,                C₁-C₆-alkoxy, C₁-C₆-haloalkoxy; preferably H, halogen,                C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy or                C₁-C₆-haloalkoxy;            -   particularly preferred H, halogen or C₁-C₆-alkyl;            -   especially preferred H, F, C, or CH₃;            -   more preferred H;        -   particularly preferred is selected from the group consisting            of Z¹, Z², Z⁴, Z⁵, Z⁶, Z⁷, Z⁸, Z⁹, Z¹⁰, Z¹¹ and Z²¹ as            defined above, wherein R^(a), R^(b), R^(c), R^(d) and Re            independently of one another are            -   H, halogen, CN, C₁-C₆-alkyl, C₁-C₆-haloalkyl,                C₁-C₆-alkoxy, C₁-C₆-haloalkoxy; preferably H, halogen,                C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy or                C₁-C₆-haloalkoxy;            -   particularly preferred H, halogen or C₁-C₆-alkyl;            -   especially preferred H, F, C, or CH₃;            -   more preferred H;        -   more particularly preferred is selected from the group            consisting of Z¹, Z⁴, Z⁵, Z⁶, Z⁷, and Z²¹ as defined above,            wherein        -   R^(a), R^(b), R^(c), R^(d) and Re independently of one            another are            -   H, halogen, CN, C₁-C₆-alkyl, C₁-C₆-haloalkyl,                C₁-C₆-alkoxy, C₁-C₆-haloalkoxy; preferably H, halogen,                C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy or                C₁-C₆-haloalkoxy;            -   particularly preferred H, halogen or C₁-C₆-alkyl;            -   especially preferred H, F, C, or CH₃;            -   more preferred H;        -   especially preferred is selected from the group consisting            of Z¹, Z⁴, Z⁵, Z⁶ and Z⁷ as defined above, wherein        -   R^(a), R^(b), R^(c), R^(d) and Re independently of one            another are            -   H, halogen, CN, C₁-C₆-alkyl, C₁-C₆-haloalkyl,                C₁-C₆-alkoxy, C₁-C₆-haloalkoxy; preferably H, halogen,                C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy or                C₁-C₆-haloalkoxy;            -   particularly preferred H, halogen or C₁-C₆-alkyl;            -   especially preferred H, F, Cl, or CH₃;            -   more preferred H;        -   more preferred is selected from the group consisting of Z¹            and Z⁷ as defined above, wherein        -   R^(a), R^(b), R^(c), R^(d) and Re independently of one            another are            -   H, halogen, CN, C₁-C₆-alkyl, C₁-C₆-haloalkyl,                C₁-C₆-alkoxy, C₁-C₆-haloalkoxy; preferably H, halogen,                C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy or                C₁-C₆-haloalkoxy;            -   particularly preferred H, halogen or C₁-C₆-alkyl;            -   especially preferred H, F, C, or CH₃;            -   more preferred H.

Also preferred are the uracilpyridines of formula (I) wherein

-   -   R¹ is C₁-C₆-alkyl,    -   R² is C₁-C₄-haloalkyl,    -   R³ is H, and    -   Y is O.

Also preferred are the uracilpyridines of formula (I) wherein

-   -   R⁴ is H or F, and        -   R⁵ is F, Cl, Br or CN.

Also preferred are the uracilpyridines of formula (I) wherein

-   -   R⁴ is H or F, and    -   R⁵ is F, Cl or CN.

Also preferred are the uracilpyridines of formula (I) wherein

-   -   R⁶ is H, C₁-C₃-alkyl or C₁-C₃-alkoxy, and    -   R⁷ is H.

Also preferred are the uracilpyridines of formula (I) wherein

-   -   R⁸ is OR⁹, NR⁹S(O)₂R¹⁰ or NR⁹S(O)₂NR¹⁰R¹¹, wherein        -   R⁹ is hydrogen, C₁-C₆-alkyl, C₃-C₆-alkenyl, C₃-C₆-alkynyl,            C₁-C₆-haloalkyl, C₁-C₆-alkoxy-C₁-C₆-alkyl,            di(C₁-C₆-alkoxy)C₁-C₆-alkyl,            C₁-C₆-alkylcarbonyl-C₁-C₆-alkyl,            C₁-C₆-alkoxycarbonyl-C₁-C₆-alkyl or            C₃-C₆-cycloalkyl-C₁-C₆-alkyl; and        -   R¹⁰, R¹¹ are C₁-C₆-alkyl.

Also preferred are the uracilpyridines of formula (I) wherein

-   -   n is 1.

Also preferred are the uracilpyridines of formula (I) wherein

-   -   Q, W and X are O.

Also preferred are the uracilpyridines of formula (I) wherein

-   -   R¹ is hydrogen, NH₂ or C₁-C₆-alkyl;    -   R² is C₁-C₆-alkyl or C₁-C₆-haloalkyl;    -   R³ is H;    -   R⁴ is H or halogen;    -   R⁵ is halogen or CN;    -   R⁶ is H, C₁-C₃-alkyl, C₁-C₃-haloalkyl, C₁-C₃-alkoxy,        C₁-C₃-haloalkoxy or C₁-C₃-alkylthio;    -   R⁷ is H;    -   R⁸ is OR⁹, SR⁹, NR¹⁰R¹¹, NR⁹S(O)₂R¹⁰ or NR⁹S(O)₂NR¹⁰R¹¹; wherein        -   R⁹ is hydrogen, C₁-C₆-alkyl, C₃-C₆-alkenyl, C₃-C₆-alkynyl,            C₁-C₆-haloalkyl, C₃-C₆-haloalkenyl, C₃-C₆-haloalkynyl,            C₁-C₆-cyanoalkyl, C₁-C₆-alkoxy-C₁-C₆-alkyl,            C₁-C₆-alkoxy-C₁-C₆-alkoxy-C₁-C₆-alkyl,            di(C₁-C₆-alkoxy)C₁-C₆-alkyl, C₁-C₆-haloalkoxy-C₁-C₆-alkyl,            C₃-C₆-alkenyloxy-C₁-C₆-alkyl,            C₃-C₆-haloalkenyloxy-C₁-C₆-alkyl,            C₃-C₆-alkenyloxy-C₁-C₆-alkoxy-C₁-C₆-alkyl,            C₁-C₆-alkylthio-C₁-C₆-alkyl,            C₁-C₆-alkylsulfinyl-C₁-C₆-alkyl,            C₁-C₆-alkylsulfonyl-C₁-C₆-alkyl,            C₁-C₆-alkylcarbonyl-C₁-C₆-alkyl,            C₁-C₆-alkoxycarbonyl-C₁-C₆-alkyl,            C₁-C₆-haloalkoxycarbonyl-C₁-C₆-alkyl,            C₃-C₆-alkenyloxycarbonyl-C₁-C₆-alkyl, amino,            (C₁-C₆-alkyl)amino, di(C₁-C₆-alkyl)amino,            (C₁-C₆-alkylcarbonyl)amino, amino-C₁-C₆-alkyl,            (C₁-C₆-alkyl)amino-C₁-C₆-alkyl,            di(C₁-C₆-alkyl)amino-C₁-C₆-alkyl, aminocarbonyl-C₁-C₆-alkyl,            (C₁-C₆-alkyl)amino-carbonyl-C₁-C₆-alkyl,            di(C₁-C₆-alkyl)aminocarbonyl-C₁-C₆-alkyl,            -   —N═CR¹²R¹³                -   wherein R¹² and R¹³ independently of one another are                    H, C₁-C₄-alkyl or phenyl;            -   C₃-C₆-cycloalkyl, C₃-C₆-cycloalkyl-C₁-C₆-alkyl,                C₃-C₆-heterocyclyl, phenyl, phenyl-C₁-C₄-alkyl or a 5-                or 6 membered heteroaryl,                -   wherein each cycloalkyl, heterocyclyl, phenyl or                    heteroaryl ring can be substituted by one to four                    substituents selected from R¹⁴ or a 3- to 7-membered                    carbocyclus,                -    which carbocyclus optionally has in addition to                    carbon atoms one or two ring members selected from                    the group consisting of —N(R¹²)—, —N═N—, —C(═O)—,                    —O— and —S—, and                -    which carbocyclus is optionally substituted with                    one to four substituents selected from R¹⁴;        -   R¹⁰ is C₁-C₆-alkyl;        -   R¹¹ is H or C₁-C₆-alkyl;        -   R¹² is phenyl or CH₃;        -   R¹³ is phenyl or CH₃;        -   R¹⁴ is halogen or C₁-C₆-alkyl;    -   n is 1 or 2;    -   Q is O, S, SO, SO₂, NH or (C₁-C₃-alkyl)N;    -   W is O;    -   X is O;    -   Y is O;    -   Z Z¹, Z², Z³, Z⁴, Z⁵, Z⁶, Z⁷, Z⁸, Z⁹, Z¹⁰, Z¹¹, Z¹², Z¹³ and Z²¹        as defined above, wherein        -   R^(a), R^(b), R^(c), R^(d) and Re independently of one            another are H, halogen, CN, C₁-C₆-alkyl, C₁-C₆-haloalkyl,            C₁-C₆-alkoxy, C₁-C₆-haloalkoxy;

particularly preferred are the uracilpyridines of formula (I) wherein

-   -   R¹ is NH₂ or C₁-C₄-alkyl;    -   R² is C₁-C₄-alkyl or C₁-C₄-haloalkyl;    -   R³ is H;    -   R⁴ is H or halogen;    -   R⁵ is halogen or CN;    -   R⁶ is H, C₁-C₃-alkyl, C₁-C₃-haloalkyl or C₁-C₃-alkoxy;    -   R⁷ is H;    -   R⁸ OR⁹, NR¹⁰R¹¹, NR⁹S(O)₂R¹⁰ or NR⁹S(O)₂NR¹⁰R¹¹; wherein        -   R⁹ is hydrogen, C₁-C₆-alkyl, C₃-C₆-alkenyl, C₃-C₆-alkynyl,            C₁-C₆-haloalkyl, C₁-C₆-alkoxy-C₁-C₆-alkyl,            di(C₁-C₆-alkoxy)C₁-C₆-alkyl,            C₁-C₆-alkylcarbonyl-C₁-C₆-alkyl,            C₁-C₆-alkoxycarbonyl-C₁-C₆-alkyl or            C₃-C₆-cycloalkyl-C₁-C₆-alkyl;        -   R¹⁰ is C₁-C₆-alkyl;        -   R¹¹ is H or C₁-C₆-alkyl;    -   n is 1;    -   Q is O, S, SO, SO₂, NH or (C₁-C₃-alkyl)N;    -   W is O;    -   X is O;    -   Y is O;    -   Z is selected from the group consisting of Z¹, Z², Z⁴, Z⁵, Z⁶,        Z⁷, Z⁸, Z⁹, Z¹⁰, Z¹¹ and Z²¹ as defined above, wherein R^(a),        R^(b), R^(c), R^(d) and Re independently of one another are H,        halogen, CN, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy,        C₁-C₆-haloalkoxy;

especially preferred are the uracilpyridines of formula (I) wherein

-   -   R¹ is NH₂ or CH₃;    -   R² is C₁-C₄-haloalkyl;    -   R³ is H;    -   R⁴ is H, F or Cl;    -   R⁵ is F, Cl, Br or CN;    -   R⁶ is H, C₁-C₃-alkyl or C₁-C₃-alkoxy;    -   R⁷ is H;    -   R⁸ is OR⁹ or NR⁹S(O)₂R¹⁰, wherein        -   R⁹ is hydrogen, C₁-C₆-alkyl, C₃-C₆-alkenyl, C₃-C₆-alkynyl or            C₁-C₆-haloalkyl, and        -   R¹⁰ is C₁-C₆-alkyl;    -   n is 1;    -   Q is O or S;    -   W is O;    -   X is O;    -   Y is O;    -   Z is selected from the group consisting of Z¹, Z⁴, Z⁵, Z⁶, Z⁷        and Z²¹ as defined above, wherein R^(a), R^(b), R^(c), R^(d) and        Re independently of one another are H, halogen, CN, C₁-C₆-alkyl,        C₁-C₆-haloalkyl, C₁-C₆-alkoxy, C₁-C₆-haloalkoxy;

also especially preferred are the uracilpyridines of formula (I) wherein

-   -   R¹ is NH₂ or CH₃;    -   R² is C₁-C₄-haloalkyl;    -   R³ is H;    -   R⁴ is H, F or Cl;    -   R⁵ is F, Cl or CN;    -   R⁶ is H, C₁-C₃-alkyl or C₁-C₃-alkoxy;    -   R⁷ is H;    -   R⁸ is OR⁹ or NR⁹S(O)₂R¹⁰, wherein        -   R⁹ is hydrogen, C₁-C₆-alkyl, C₃-C₆-alkenyl, C₃-C₆-alkynyl or            C₁-C₆-haloalkyl, and        -   R¹⁰ is C₁-C₆-alkyl;    -   n is 1;    -   Q is O or S;    -   W is O;    -   X is O;    -   Y is O;    -   Z is selected from the group consisting of Z¹, Z⁴, Z⁵, Z⁶ and Z⁷        as defined above, wherein R^(a), R^(b), R^(c), R^(d) and Re        independently of one another are H, halogen, CN, C₁-C₆-alkyl,        C₁-C₆-haloalkyl, C₁-C₆-alkoxy, C₁-C₆-haloalkoxy;

more preferred are the uracilpyridines of formula (I) wherein

-   -   R¹ is CH₃;    -   R² is CF₃;    -   R³ is H;    -   R⁴ is H, F or Cl;    -   R⁵ is F, Cl, Br or CN;    -   R⁶ is H, CH₃ or OCH₃;    -   R⁷ is H;    -   R⁸ is OR⁹ or NR⁹S(O)₂R¹⁰; wherein        -   R⁹ is hydrogen, C₁-C₆-alkyl, C₃-C₆-alkenyl, or            C₃-C₆-alkynyl, and        -   R¹⁰ is C₁-C₆-alkyl;    -   n is 1;    -   Q is O;    -   W is O;    -   X is O;    -   Y is O;    -   Z is selected from the group consisting of Z¹ and Z⁷ as defined        above, wherein R^(a), R^(b), R^(c), R^(d) and R^(e)        independently of one another are H, halogen, CN, C₁-C₆-alkyl,        C₁-C₆-haloalkyl, C₁-C₆-alkoxy, C₁-C₆-haloalkoxy.

also more preferred are the uracilpyridines of formula (I) wherein

-   -   R¹ is CH₃;    -   R² is CF₃;    -   R³ is H;    -   R⁴ is H, F or Cl;    -   R⁵ is F, Cl or CN;    -   R⁶ is H, CH₃ or OCH₃;    -   R⁷ is H;    -   R⁸ is OR⁹ or NR⁹S(O)₂R¹⁰; wherein        -   R⁹ is hydrogen, C₁-C₆-alkyl, or C₃-C₆-alkynyl, and        -   R¹⁰ is C₁-C₆-alkyl;    -   n is 1;    -   Q is O;    -   W is O;    -   X is O;    -   Y is O;    -   Z is selected from the group consisting of Z¹ and Z⁷ as defined        above, wherein R^(a), R^(b), R^(c), R^(d) and R^(e)        independently of one another are H, halogen, CN, C₁-C₆-alkyl,        C₁-C₆-haloalkyl, C₁-C₆-alkoxy, C₁-C₆-haloalkoxy.

Also preferred are the uracilpyridines of formula (I) wherein

-   -   R¹ is CH₃;    -   R² is CF₃;    -   R³ is H;    -   R⁴ is H, F or Cl;    -   R⁵ is F, Cl, Br or CN;    -   R⁶ is H, CH₃ or OCH₃;    -   R⁷ is H;    -   R⁸ OR⁹, SR⁹, NR¹⁰R¹¹, NR⁹OR⁹, NR⁹S(O)₂R¹⁰ or NR⁹S(O)₂NR¹⁰R¹¹,        wherein        -   R⁹ is hydrogen, C₁-C₆-alkyl, C₃-C₆-alkenyl, C₃-C₆-alkynyl,            C₁-C₆-haloalkyl, C₃-C₆-haloalkenyl, C₃-C₆-haloalkynyl,            C₁-C₆-cyanoalkyl, C₁-C₆-alkoxy-C₁-C₆-alkyl,            C₁-C₆-alkoxy-C₁-C₆-alkoxy-C₁-C₆-alkyl,            di(C₁-C₆-alkoxy)C₁-C₆-alkyl, C₁-C₆-haloalkoxy-C₁-C₆-alkyl,            C₃-C₆-alkenyloxy-C₁-C₆-alkyl,            C₃-C₆-haloalkenyloxy-C₁-C₆-alkyl,            C₃-C₆-alkenyloxy-C₁-C₆-alkoxy-C₁-C₆-alkyl,            C₁-C₆-alkylthio-C₁-C₆-alkyl,            C₁-C₆-alkylsulfinyl-C₁-C₆-alkyl,            C₁-C₆-alkylsulfonyl-C₁-C₆-alkyl,            C₁-C₆-alkylcarbonyl-C₁-C₆-alkyl,            C₁-C₆-alkoxycarbonyl-C₁-C₆-alkyl,            C₁-C₆-haloalkoxycarbonyl-C₁-C₆-alkyl,            C₃-C₆-alkenyloxycarbonyl-C₁-C₆-alkyl,            C₃-C₆-alkynyloxycarbonyl-C₁-C₆-alkyl, amino,            (C₁-C₆-alkyl)amino, di(C₁-C₆-alkyl)amino,            (C₁-C₆-alkylcarbonyl)amino, amino-C₁-C₆-alkyl,            (C₁-C₆-alkyl)amino-C₁-C₆-alkyl,            di(C₁-C₆-alkyl)amino-C₁-C₆-alkyl, aminocarbonyl-C₁-C₆-alkyl,            (C₁-C₆-alkyl)aminocarbonyl-C₁-C₆-alkyl,            di(C₁-C₆-alkyl)aminocarbonyl-C₁-C₆-alkyl,            -   —N═CR¹²R¹³, wherein R¹² and R¹³ independently of one                another are H, C₁-C₄-alkyl or phenyl;            -   C₃-C₆-cycloalkyl, C₃-C₆-cycloalkyl-C₁-C₆-alkyl,                C₃-C₆-heterocyclyl, C₃-C₆-heterocyclyl-C₁-C₆-alkyl,                phenyl, phenyl-C₁-C₄-alkyl or a 5- or 6 membered                heteroaryl,                -   wherein each cycloalkyl, heterocyclyl, phenyl or                    heteroaryl ring can be substituted by one to four                    substituents selected from R¹⁴ or a 3- to 7-membered                    carbocyclus,                -    which carbocyclus optionally has in addition to                    carbon atoms one or two ring members selected from                    the group consisting of                -    —N(R¹²)—, —N═N—, —C(═O)—, —O— and —S—, and                -    which carbocyclus is optionally substituted with                    one to four substituents selected from R¹⁴;                -    wherein R¹⁴ is halogen, NO₂, CN, C₁-C₄-alkyl,                    C₁-C₄-haloalkyl, C₁-C₄-alkoxy or                    C₁-C₄-alkoxycarbonyl;        -   R¹⁰, R¹¹ independently of one another are R⁹, or together            form a 3- to 7-membered carbocyclus,            -   which carbocyclus optionally has in addition to carbon                atoms one or two ring members selected from the group                consisting of —N(R¹²)—, —N═N—, —C(═O)—, —O— and —S—, and            -   which carbocyclus is optionally substituted with one to                four substituents selected from R¹⁴;    -   n is 1;    -   Q is O;    -   W is O;    -   X is O;    -   Y is O;    -   Z is selected from the group consisting of Z¹ and Z⁷ as defined        above, wherein R^(a), R^(b), R^(c), R^(d) and R^(e)        independently of one another are H, halogen, CN, C₁-C₆-alkyl,        C₁-C₆-haloalkyl, C₁-C₆-alkoxy, C₁-C₆-haloalkoxy.

Also preferred are the uracilpyridines of formula (I) wherein

-   -   R¹ is CH₃;    -   R² is CF₃;    -   R³ is H;    -   R⁴ is H, F or Cl;    -   R⁵ is F, Cl or CN;    -   R⁶ is H, CH₃ or OCH₃;    -   R⁷ is H;    -   R⁸ OR⁹, SR⁹, NR¹⁰R¹¹, NR⁹OR⁹, NR⁹S(O)₂R¹⁰ or NR⁹S(O)₂NR¹⁰R¹¹,        wherein        -   R⁹ is hydrogen, C₁-C₆-alkyl, C₃-C₆-alkenyl, C₃-C₆-alkynyl,            C₁-C₆-haloalkyl, C₃-C₆-haloalkenyl, C₃-C₆-haloalkynyl,            C₁-C₆-cyanoalkyl, C₁-C₆-alkoxy-C₁-C₆-alkyl,            C₁-C₆-alkoxy-C₁-C₆-alkoxy-C₁-C₆-alkyl,            di(C₁-C₆-alkoxy)C₁-C₆-alkyl, C₁-C₆-haloalkoxy-C₁-C₆-alkyl,            C₃-C₆-alkenyloxy-C₁-C₆-alkyl,            C₃-C₆-haloalkenyloxy-C₁-C₆-alkyl,            C₃-C₆-alkenyloxy-C₁-C₆-alkoxy-C₁-C₆-alkyl,            C₁-C₆-alkylthio-C₁-C₆-alkyl,            C₁-C₆-alkylsulfinyl-C₁-C₆-alkyl,            C₁-C₆-alkylsulfonyl-C₁-C₆-alkyl,            C₁-C₆-alkylcarbonyl-C₁-C₆-alkyl,            C₁-C₆-alkoxycarbonyl-C₁-C₆-alkyl,            C₁-C₆-haloalkoxycarbonyl-C₁-C₆-alkyl,            C₃-C₆-alkenyloxycarbonyl-C₁-C₆-alkyl,            C₃-C₆-alkynyloxycarbonyl-C₁-C₆-alkyl, amino,            (C₁-C₆-alkyl)amino, di(C₁-C₆-alkyl)amino,            (C₁-C₆-alkylcarbonyl)amino, amino-C₁-C₆-alkyl,            (C₁-C₆-alkyl)amino-C₁-C₆-alkyl,            di(C₁-C₆-alkyl)amino-C₁-C₆-alkyl, aminocarbonyl-C₁-C₆-alkyl,            (C₁-C₆-alkyl)aminocarbonyl-C₁-C₆-alkyl,            di(C₁-C₆-alkyl)aminocarbonyl-C₁-C₆-alkyl,            -   —N═CR¹²R¹³, wherein R¹² and R¹³ independently of one                another are H, C₁-C₄-alkyl or phenyl;            -   C₃-C₆-cycloalkyl, C₃-C₆-cycloalkyl-C₁-C₆-alkyl,                C₃-C₆-heterocyclyl, C₃-C₆-heterocyclyl-C₁-C₆-alkyl,                phenyl, phenyl-C₁-C₄-alkyl or a 5- or 6 membered                heteroaryl,                -   wherein each cycloalkyl, heterocyclyl, phenyl or                    heteroaryl ring can be substituted by one to four                    substituents selected from R¹⁴ or a 3- to 7-membered                    carbocyclus,                -    which carbocyclus optionally has in addition to                    carbon atoms one or two ring members selected from                    the group consisting of                -    —N(R¹²)—, —N═N—, —C(═O)—, —O— and —S—, and                -    which carbocyclus is optionally substituted with                    one to four substituents selected from R¹⁴;                -    wherein R¹⁴ is halogen, NO₂, CN, C₁-C₄-alkyl,                    C₁-C₄-haloalkyl, C₁-C₄-alkoxy or                    C₁-C₄-alkoxycarbonyl;        -   R¹⁰, R¹¹ independently of one another are R⁹, or together            form a 3- to 7-membered carbocyclus,            -   which carbocyclus optionally has in addition to carbon                atoms one or two ring members selected from the group                consisting of —N(R¹²)—, —N═N—, —C(═O)—, —O— and —S—, and            -   which carbocyclus is optionally substituted with one to                four substituents selected from R¹⁴;    -   n is 1;    -   Q is O;    -   W is O;    -   X is O;    -   Y is O;    -   Z is selected from the group consisting of Z¹ and Z⁷ as defined        above, wherein R^(a), R^(b), R^(c), R^(d) and R^(e)        independently of one another are H, halogen, CN, C₁-C₆-alkyl,        C₁-C₆-haloalkyl, C₁-C₆-alkoxy, C₁-C₆-haloalkoxy.

Particular preference is given to uracilpyrimidines of formula (I.a)(corresponds to formula (I) wherein R¹ is CH₃, R² is CF₃, R³ is H, R⁷ isH, n is 1, Q, W, X and Y are O, and Z is Z-1 as defined, wherein R^(a),R^(b), R^(c) and R^(d) are H:

-   -   wherein the variables R⁴, R⁵, R⁶ and R⁸ have the meanings, in        particular the preferred meanings, as defined above.

Special preference is given to the compounds of the formulae (I.a.1) to(I.a.672), preferably (I.a.1) to (I.a.504), of Table A, where thedefinitions of the variables R⁴, R⁵, R⁶ and R⁸ are of particularimportance for the compounds according to the invention not only incombination with one another but in each case also on their own:

TABLE A No. R⁴ R⁵ R⁶ R⁸ I.a.1 H F H OH I.a.2 H F H OCH₃ I.a.3 H F HOC₂H₅ I.a.4 H F H OCH(CH₃)₂ I.a.5 H F H OCH₂CH₂CH₃ I.a.6 H F HOCH₂CH(CH₃)₂ I.a.7 H F H OCH₂CH═CH₂ I.a.8 H F H OCH₂C≡CH I.a.9 H F HOCH₂CF₃ I.a.10 H F H OCH₂CHF₂ I.a.11 H F H OC₆H₅ I.a.12 H F H OCH₂(C₆H₅)I.a.13 H F H OCH₂OCH₃ I.a.14 H F H OCH₂OCH₂CH₃ I.a.15 H F H OCH₂CH₂OCH₃I.a.16 H F H OCH₂CH₂OCH₂CH₃ I.a.17 H F H OCH₂(CO)OCH₃ I.a.18 H F HOCH₂(CO)OCH₂CH₃ I.a.19 H F H OCH(CH₃)(CO)OCH₃ I.a.20 H F HOCH(CH₃)(CO)OCH₂CH₃ I.a.21 H F H OCH₂-cyclopropyl I.a.22 H F HOCH₂-cyclobutyl I.a.23 H F H SCH₃ I.a.24 H F H SC₂H₅ I.a.25 H F HNHSO₂CH₃ I.a.26 H F H NHSO₂CH(CH₃)₂ I.a.27 H F H NHSO₂N(CH₃)₂ I.a.28 H FH NHSO₂N(CH₃)[CH(CH₃)₂] I.a.29 H F CH₃ OH I.a.30 H F CH₃ OCH₃ I.a.31 H FCH₃ OC₂H₅ I.a.32 H F CH₃ OCH(CH₃)₂ I.a.33 H F CH₃ OCH₂CH₂CH₃ I.a.34 H FCH₃ OCH₂CH(CH₃)₂ I.a.35 H F CH₃ OCH₂CH═CH₂ I.a.36 H F CH₃ OCH₂C≡CHI.a.37 H F CH₃ OCH₂CF₃ I.a.38 H F CH₃ OCH₂CHF₂ I.a.39 H F CH₃ OC₆H₅I.a.40 H F CH₃ OCH₂(C₆H₅) I.a.41 H F CH₃ OCH₂OCH₃ I.a.42 H F CH₃OCH₂OCH₂CH₃ I.a.43 H F CH₃ OCH₂CH₂OCH₃ I.a.44 H F CH₃ OCH₂CH₂OCH₂CH₃I.a.45 H F CH₃ OCH₂(CO)OCH₃ I.a.46 H F CH₃ OCH₂(CO)OCH₂CH₃ I.a.47 H FCH₃ OCH(CH₃)(CO)OCH₃ I.a.48 H F CH₃ OCH(CH₃)(CO)OCH₂CH₃ I.a.49 H F CH₃OCH₂-cyclopropyl I.a.50 H F CH₃ OCH₂-cyclobutyl I.a.51 H F CH₃ SCH₃I.a.52 H F CH₃ SC₂H₅ I.a.53 H F CH₃ NHSO₂CH₃ I.a.54 H F CH₃NHSO₂CH(CH₃)₂ I.a.55 H F CH₃ NHSO₂N(CH₃)₂ I.a.56 H F CH₃NHSO₂N(CH₃)[CH(CH₃)₂] I.a.57 H F OCH₃ OH I.a.58 H F OCH₃ OCH₃ I.a.59 H FOCH₃ OC₂H₅ I.a.60 H F OCH₃ OCH(CH₃)₂ I.a.61 H F OCH₃ OCH₂CH₂CH₃ I.a.62 HF OCH₃ OCH₂CH(CH₃)₂ I.a.63 H F OCH₃ OCH₂CH═CH₂ I.a.64 H F OCH₃ OCH₂C≡CHI.a.65 H F OCH₃ OCH₂CF₃ I.a.66 H F OCH₃ OCH₂CHF₂ I.a.67 H F OCH₃ OC₆H₅I.a.68 H F OCH₃ OCH₂(C₆H₅) I.a.69 H F OCH₃ OCH₂OCH₃ I.a.70 H F OCH₃OCH₂OCH₂CH₃ I.a.71 H F OCH₃ OCH₂CH₂OCH₃ I.a.72 H F OCH₃ OCH₂CH₂OCH₂CH₃I.a.73 H F OCH₃ OCH₂(CO)OCH₃ I.a.74 H F OCH₃ OCH₂(CO)OCH₂CH₃ I.a.75 H FOCH₃ OCH(CH₃)(CO)OCH₃ I.a.76 H F OCH₃ OCH(CH₃)(CO)OCH₂CH₃ I.a.77 H FOCH₃ OCH₂-cyclopropyl I.a.78 H F OCH₃ OCH₂-cyclobutyl I.a.79 H F OCH₃SCH₃ I.a.80 H F OCH₃ SC₂H₅ I.a.81 H F OCH₃ NHSO₂CH₃ I.a.82 H F OCH₃NHSO₂CH(CH₃)₂ I.a.83 H F OCH₃ NHSO₂N(CH₃)₂ I.a.84 H F OCH₃NHSO₂N(CH₃)[CH(CH₃)₂] I.a.85 H Cl H OH I.a.86 H Cl H OCH₃ I.a.87 H Cl HOC₂H₅ I.a.88 H Cl H OCH(CH₃)₂ I.a.89 H Cl H OCH₂CH₂CH₃ I.a.90 H Cl HOCH₂CH(CH₃)₂ I.a.91 H Cl H OCH₂CH═CH₂ I.a.92 H Cl H OCH₂C≡CH I.a.93 H ClH OCH₂CF₃ I.a.94 H Cl H OCH₂CHF₂ I.a.95 H Cl H OC₆H₅ I.a.96 H Cl HOCH₂(C₆H₅) I.a.97 H Cl H OCH₂OCH₃ I.a.98 H Cl H OCH₂OCH₂CH₃ I.a.99 H ClH OCH₂CH₂OCH₃ I.a.100 H Cl H OCH₂CH₂OCH₂CH₃ I.a.101 H Cl H OCH₂(CO)OCH₃I.a.102 H Cl H OCH₂(CO)OCH₂CH₃ I.a.103 H Cl H OCH(CH₃)(CO)OCH₃ I.a.104 HCl H OCH(CH₃)(CO)OCH₂CH₃ I.a.105 H Cl H OCH₂-cyclopropyl I.a.106 H Cl HOCH₂-cyclobutyl I.a.107 H Cl H SCH₃ I.a.108 H Cl H SC₂H₅ I.a.109 H Cl HNHSO₂CH₃ I.a.110 H Cl H NHSO₂CH(CH₃)₂ I.a.111 H Cl H NHSO₂N(CH₃)₂I.a.112 H Cl H NHSO₂N(CH₃)[CH(CH₃)₂] I.a.113 H Cl CH₃ OH I.a.114 H ClCH₃ OCH₃ I.a.115 H Cl CH₃ OC₂H₅ I.a.116 H Cl CH₃ OCH(CH₃)₂ I.a.117 H ClCH₃ OCH₂CH₂CH₃ I.a.118 H Cl CH₃ OCH₂CH(CH₃)₂ I.a.119 H Cl CH₃ OCH₂CH═CH₂I.a.120 H Cl CH₃ OCH₂C≡CH I.a.121 H Cl CH₃ OCH₂CF₃ I.a.122 H Cl CH₃OCH₂CHF₂ I.a.123 H Cl CH₃ OC₆H₅ I.a.124 H Cl CH₃ OCH₂(C₆H₅) I.a.125 H ClCH₃ OCH₂OCH₃ I.a.126 H Cl CH₃ OCH₂OCH₂CH₃ I.a.127 H Cl CH₃ OCH₂CH₂OCH₃I.a.128 H Cl CH₃ OCH₂CH₂OCH₂CH₃ I.a.129 H Cl CH₃ OCH₂(CO)OCH₃ I.a.130 HCl CH₃ OCH₂(CO)OCH₂CH₃ I.a.131 H Cl CH₃ OCH(CH₃)(CO)OCH₃ I.a.132 H ClCH₃ OCH(CH₃)(CO)OCH₂CH₃ I.a.133 H Cl CH₃ OCH₂-cyclopropyl I.a.134 H ClCH₃ OCH₂-cyclobutyl I.a.135 H Cl CH₃ SCH₃ I.a.136 H Cl CH₃ SC₂H₅ I.a.137H Cl CH₃ NHSO₂CH₃ I.a.138 H Cl CH₃ NHSO₂CH(CH₃)₂ I.a.139 H Cl CH₃NHSO₂N(CH₃)₂ I.a.140 H Cl CH₃ NHSO₂N(CH₃)[CH(CH₃)₂] I.a.141 H Cl OCH₃ OHI.a.142 H Cl OCH₃ OCH₃ I.a.143 H Cl OCH₃ OC₂H₅ I.a.144 H Cl OCH₃OCH(CH₃)₂ I.a.145 H Cl OCH₃ OCH₂CH₂CH₃ I.a.146 H Cl OCH₃ OCH₂CH(CH₃)₂I.a.147 H Cl OCH₃ OCH₂CH═CH₂ I.a.148 H Cl OCH₃ OCH₂C≡CH I.a.149 H ClOCH₃ OCH₂CF₃ I.a.150 H Cl OCH₃ OCH₂CHF₂ I.a.151 H Cl OCH₃ OC₆H₅ I.a.152H Cl OCH₃ OCH₂(C₆H₅) I.a.153 H Cl OCH₃ OCH₂OCH₃ I.a.154 H Cl OCH₃OCH₂OCH₂CH₃ I.a.155 H Cl OCH₃ OCH₂CH₂OCH₃ I.a.156 H Cl OCH₃OCH₂CH₂OCH₂CH₃ I.a.157 H Cl OCH₃ OCH₂(CO)OCH₃ I.a.158 H Cl OCH₃OCH₂(CO)OCH₂CH₃ I.a.159 H Cl OCH₃ OCH(CH₃)(CO)OCH₃ I.a.160 H Cl OCH₃OCH(CH₃)(CO)OCH₂CH₃ I.a.161 H Cl OCH₃ OCH₂-cyclopropyl I.a.162 H Cl OCH₃OCH₂-cyclobutyl I.a.163 H Cl OCH₃ SCH₃ I.a.164 H Cl OCH₃ SC₂H₅ I.a.165 HCl OCH₃ NHSO₂CH₃ I.a.166 H Cl OCH₃ NHSO₂CH(CH₃)₂ I.a.167 H Cl OCH₃NHSO₂N(CH₃)₂ I.a.168 H Cl OCH₃ NHSO₂N(CH₃)[CH(CH₃)₂] I.a.169 H CN H OHI.a.170 H CN H OCH₃ I.a.171 H CN H OC₂H₅ I.a.172 H CN H OCH(CH₃)₂I.a.173 H CN H OCH₂CH₂CH₃ I.a.174 H CN H OCH₂CH(CH₃)₂ I.a.175 H CN HOCH₂CH═CH₂ I.a.176 H CN H OCH₂C≡CH I.a.177 H CN H OCH₂CF₃ I.a.178 H CN HOCH₂CHF₂ I.a.179 H CN H OC₆H₅ I.a.180 H CN H OCH₂(C₆H₅) I.a.181 H CN HOCH₂OCH₃ I.a.182 H CN H OCH₂OCH₂CH₃ I.a.183 H CN H OCH₂CH₂OCH₃ I.a.184 HCN H OCH₂CH₂OCH₂CH₃ I.a.185 H CN H OCH₂(CO)OCH₃ I.a.186 H CN HOCH₂(CO)OCH₂CH₃ I.a.187 H CN H OCH(CH₃)(CO)OCH₃ I.a.188 H CN HOCH(CH₃)(CO)OCH₂CH₃ I.a.189 H CN H OCH₂-cyclopropyl I.a.190 H CN HOCH₂-cyclobutyl I.a.191 H CN H SCH₃ I.a.192 H CN H SC₂H₅ I.a.193 H CN HNHSO₂CH₃ I.a.194 H CN H NHSO₂CH(CH₃)₂ I.a.195 H CN H NHSO₂N(CH₃)₂I.a.196 H CN H NHSO₂N(CH₃)[CH(CH₃)₂] I.a.197 H CN CH₃ OH I.a.198 H CNCH₃ OCH₃ I.a.199 H CN CH₃ OC₂H₅ I.a.200 H CN CH₃ OCH(CH₃)₂ I.a.201 H CNCH₃ OCH₂CH₂CH₃ I.a.202 H CN CH₃ OCH₂CH(CH₃)₂ I.a.203 H CN CH₃ OCH₂CH═CH₂I.a.204 H CN CH₃ OCH₂C≡CH I.a.205 H CN CH₃ OCH₂CF₃ I.a.206 H CN CH₃OCH₂CHF₂ I.a.207 H CN CH₃ OC₆H₅ I.a.208 H CN CH₃ OCH₂(C₆H₅) I.a.209 H CNCH₃ OCH₂OCH₃ I.a.210 H CN CH₃ OCH₂OCH₂CH₃ I.a.211 H CN CH₃ OCH₂CH₂OCH₃I.a.212 H CN CH₃ OCH₂CH₂OCH₂CH₃ I.a.213 H CN CH₃ OCH₂(CO)OCH₃ I.a.214 HCN CH₃ OCH₂(CO)OCH₂CH₃ I.a.215 H CN CH₃ OCH(CH₃)(CO)OCH₃ I.a.216 H CNCH₃ OCH(CH₃)(CO)OCH₂CH₃ I.a.217 H CN CH₃ OCH₂-cyclopropyl I.a.218 H CNCH₃ OCH₂-cyclobutyl I.a.219 H CN CH₃ SCH₃ I.a.220 H CN CH₃ SC₂H₅ I.a.221H CN CH₃ NHSO₂CH₃ I.a.222 H CN CH₃ NHSO₂CH(CH₃)₂ I.a.223 H CN CH₃NHSO₂N(CH₃)₂ I.a.224 H CN CH₃ NHSO₂N(CH₃)[CH(CH₃)₂] I.a.225 H CN OCH₃ OHI.a.226 H CN OCH₃ OCH₃ I.a.227 H CN OCH₃ OC₂H₅ I.a.228 H CN OCH₃OCH(CH₃)₂ I.a.229 H CN OCH₃ OCH₂CH₂CH₃ I.a.230 H CN OCH₃ OCH₂CH(CH₃)₂I.a.231 H CN OCH₃ OCH₂CH═CH₂ I.a.232 H CN OCH₃ OCH₂C≡CH I.a.233 H CNOCH₃ OCH₂CF₃ I.a.234 H CN OCH₃ OCH₂CHF₂ I.a.235 H CN OCH₃ OC₆H₅ I.a.236H CN OCH₃ OCH₂(C₆H₅) I.a.237 H CN OCH₃ OCH₂OCH₃ I.a.238 H CN OCH₃OCH₂OCH₂CH₃ I.a.239 H CN OCH₃ OCH₂CH₂OCH₃ I.a.240 H CN OCH₃OCH₂CH₂OCH₂CH₃ I.a.241 H CN OCH₃ OCH₂(CO)OCH₃ I.a.242 H CN OCH₃OCH₂(CO)OCH₂CH₃ I.a.243 H CN OCH₃ OCH(CH₃)(CO)OCH₃ I.a.244 H CN OCH₃OCH(CH₃)(CO)OCH₂CH₃ I.a.245 H CN OCH₃ OCH₂-cyclopropyl I.a.246 H CN OCH₃OCH₂-cyclobutyl I.a.247 H CN OCH₃ SCH₃ I.a.248 H CN OCH₃ SC₂H₅ I.a.249 HCN OCH₃ NHSO₂CH₃ I.a.250 H CN OCH₃ NHSO₂CH(CH₃)₂ I.a.251 H CN OCH₃NHSO₂N(CH₃)₂ I.a.252 H CN OCH₃ NHSO₂N(CH₃)[CH(CH₃)₂] I.a.253 F F H OHI.a.254 F F H OCH₃ I.a.255 F F H OC₂H₅ I.a.256 F F H OCH(CH₃)₂ I.a.257 FF H OCH₂CH₂CH₃ I.a.258 F F H OCH₂CH(CH₃)₂ I.a.259 F F H OCH₂CH═CH₂I.a.260 F F H OCH₂C≡CH I.a.261 F F H OCH₂CF₃ I.a.262 F F H OCH₂CHF₂I.a.263 F F H OC₆H₅ I.a.264 F F H OCH₂(C₆H₅) I.a.265 F F H OCH₂OCH₃I.a.266 F F H OCH₂OCH₂CH₃ I.a.267 F F H OCH₂CH₂OCH₃ I.a.268 F F HOCH₂CH₂OCH₂CH₃ I.a.269 F F H OCH₂(CO)OCH₃ I.a.270 F F H OCH₂(CO)OCH₂CH₃I.a.271 F F H OCH(CH₃)(CO)OCH₃ I.a.272 F F H OCH(CH₃)(CO)OCH₂CH₃ I.a.273F F H OCH₂-cyclopropyl I.a.274 F F H OCH₂-cyclobutyl I.a.275 F F H SCH₃I.a.276 F F H SC₂H₅ I.a.277 F F H NHSO₂CH₃ I.a.278 F F H NHSO₂CH(CH₃)₂I.a.279 F F H NHSO₂N(CH₃)₂ I.a.280 F F H NHSO₂N(CH₃)[CH(CH₃)₂] I.a.281 FF CH₃ OH I.a.282 F F CH₃ OCH₃ I.a.283 F F CH₃ OC₂H₅ I.a.284 F F CH₃OCH(CH₃)₂ I.a.285 F F CH₃ OCH₂CH₂CH₃ I.a.286 F F CH₃ OCH₂CH(CH₃)₂I.a.287 F F CH₃ OCH₂CH═CH₂ I.a.288 F F CH₃ OCH₂C≡CH I.a.289 F F CH₃OCH₂CF₃ I.a.290 F F CH₃ OCH₂CHF₂ I.a.291 F F CH₃ OC₆H₅ I.a.292 F F CH₃OCH₂(C₆H₅) I.a.293 F F CH₃ OCH₂OCH₃ I.a.294 F F CH₃ OCH₂OCH₂CH₃ I.a.295F F CH₃ OCH₂CH₂OCH₃ I.a.296 F F CH₃ OCH₂CH₂OCH₂CH₃ I.a.297 F F CH₃OCH₂(CO)OCH₃ I.a.298 F F CH₃ OCH₂(CO)OCH₂CH₃ I.a.299 F F CH₃OCH(CH₃)(CO)OCH₃ I.a.300 F F CH₃ OCH(CH₃)(CO)OCH₂CH₃ I.a.301 F F CH₃OCH₂-cyclopropyl I.a.302 F F CH₃ OCH₂-cyclobutyl I.a.303 F F CH₃ SCH₃I.a.304 F F CH₃ SC₂H₅ I.a.305 F F CH₃ NHSO₂CH₃ I.a.306 F F CH₃NHSO₂CH(CH₃)₂ I.a.307 F F CH₃ NHSO₂N(CH₃)₂ I.a.308 F F CH₃NHSO₂N(CH₃)[CH(CH₃)₂] I.a.309 F F OCH₃ OH I.a.310 F F OCH₃ OCH₃ I.a.311F F OCH₃ OC₂H₅ I.a.312 F F OCH₃ OCH(CH₃)₂ I.a.313 F F OCH₃ OCH₂CH₂CH₃I.a.314 F F OCH₃ OCH₂CH(CH₃)₂ I.a.315 F F OCH₃ OCH₂CH═CH₂ I.a.316 F FOCH₃ OCH₂C≡CH I.a.317 F F OCH₃ OCH₂CF₃ I.a.318 F F OCH₃ OCH₂CHF₂ I.a.319F F OCH₃ OC₆H₅ I.a.320 F F OCH₃ OCH₂(C₆H₅) I.a.321 F F OCH₃ OCH₂OCH₃I.a.322 F F OCH₃ OCH₂OCH₂CH₃ I.a.323 F F OCH₃ OCH₂CH₂OCH₃ I.a.324 F FOCH₃ OCH₂CH₂OCH₂CH₃ I.a.325 F F OCH₃ OCH₂(CO)OCH₃ I.a.326 F F OCH₃OCH₂(CO)OCH₂CH₃ I.a.327 F F OCH₃ OCH(CH₃)(CO)OCH₃ I.a.328 F F OCH₃OCH(CH₃)(CO)OCH₂CH₃ I.a.329 F F OCH₃ OCH₂-cyclopropyl I.a.330 F F OCH₃OCH₂-cyclobutyl I.a.331 F F OCH₃ SCH₃ I.a.332 F F OCH₃ SC₂H₅ I.a.333 F FOCH₃ NHSO₂CH₃ I.a.334 F F OCH₃ NHSO₂CH(CH₃)₂ I.a.335 F F OCH₃NHSO₂N(CH₃)₂ I.a.336 F F OCH₃ NHSO₂N(CH₃)[CH(CH₃)₂] I.a.337 F Cl H OHI.a.338 F Cl H OCH₃ I.a.339 F Cl H OC₂H₅ I.a.340 F Cl H OCH(CH₃)₂I.a.341 F Cl H OCH₂CH₂CH₃ I.a.342 F Cl H OCH₂CH(CH₃)₂ I.a.343 F Cl HOCH₂CH═CH₂ I.a.344 F Cl H OCH₂C≡CH I.a.345 F Cl H OCH₂CF₃ I.a.346 F Cl HOCH₂CHF₂ I.a.347 F Cl H OC₆H₅ I.a.348 F Cl H OCH₂(C₆H₅) I.a.349 F Cl HOCH₂OCH₃ I.a.350 F Cl H OCH₂OCH₂CH₃ I.a.351 F Cl H OCH₂CH₂OCH₃ I.a.352 FCl H OCH₂CH₂OCH₂CH₃ I.a.353 F Cl H OCH₂(CO)OCH₃ I.a.354 F Cl HOCH₂(CO)OCH₂CH₃ I.a.355 F Cl H OCH(CH₃)(CO)OCH₃ I.a.356 F Cl HOCH(CH₃)(CO)OCH₂CH₃ I.a.357 F Cl H OCH₂-cyclopropyl I.a.358 F Cl HOCH₂-cyclobutyl I.a.359 F Cl H SCH₃ I.a.360 F Cl H SC₂H₅ I.a.361 F Cl HNHSO₂CH₃ I.a.362 F Cl H NHSO₂CH(CH₃)₂ I.a.363 F Cl H NHSO₂N(CH₃)₂I.a.364 F Cl H NHSO₂N(CH₃)[CH(CH₃)₂] I.a.365 F Cl CH₃ OH I.a.366 F ClCH₃ OCH₃ I.a.367 F Cl CH₃ OC₂H₅ I.a.368 F Cl CH₃ OCH(CH₃)₂ I.a.369 F ClCH₃ OCH₂CH₂CH₃ I.a.370 F Cl CH₃ OCH₂CH(CH₃)₂ I.a.371 F Cl CH₃ OCH₂CH═CH₂I.a.372 F Cl CH₃ OCH₂C≡CH I.a.373 F Cl CH₃ OCH₂CF₃ I.a.374 F Cl CH₃OCH₂CHF₂ I.a.375 F Cl CH₃ OC₆H₅ I.a.376 F Cl CH₃ OCH₂(C₆H₅) I.a.377 F ClCH₃ OCH₂OCH₃ I.a.378 F Cl CH₃ OCH₂OCH₂CH₃ I.a.379 F Cl CH₃ OCH₂CH₂OCH₃I.a.380 F Cl CH₃ OCH₂CH₂OCH₂CH₃ I.a.381 F Cl CH₃ OCH₂(CO)OCH₃ I.a.382 FCl CH₃ OCH₂(CO)OCH₂CH₃ I.a.383 F Cl CH₃ OCH(CH₃)(CO)OCH₃ I.a.384 F ClCH₃ OCH(CH₃)(CO)OCH₂CH₃ I.a.385 F Cl CH₃ OCH₂-cyclopropyl I.a.386 F ClCH₃ OCH₂-cyclobutyl I.a.387 F Cl CH₃ SCH₃ I.a.388 F Cl CH₃ SC₂H₅ I.a.389F Cl CH₃ NHSO₂CH₃ I.a.390 F Cl CH₃ NHSO₂CH(CH₃)₂ I.a.391 F Cl CH₃NHSO₂N(CH₃)₂ I.a.392 F Cl CH₃ NHSO₂N(CH₃)[CH(CH₃)₂] I.a.393 F Cl OCH₃ OHI.a.394 F Cl OCH₃ OCH₃ I.a.395 F Cl OCH₃ OC₂H₅ I.a.396 F Cl OCH₃OCH(CH₃)₂ I.a.397 F Cl OCH₃ OCH₂CH₂CH₃ I.a.398 F Cl OCH₃ OCH₂CH(CH₃)₂I.a.399 F Cl OCH₃ OCH₂CH═CH₂ I.a.400 F Cl OCH₃ OCH₂C≡CH I.a.401 F ClOCH₃ OCH₂CF₃ I.a.402 F Cl OCH₃ OCH₂CHF₂ I.a.403 F Cl OCH₃ OC₆H₅ I.a.404F Cl OCH₃ OCH₂(C₆H₅) I.a.405 F Cl OCH₃ OCH₂OCH₃ I.a.406 F Cl OCH₃OCH₂OCH₂CH₃ I.a.407 F Cl OCH₃ OCH₂CH₂OCH₃ I.a.408 F Cl OCH₃OCH₂CH₂OCH₂CH₃ I.a.409 F Cl OCH₃ OCH₂(CO)OCH₃ I.a.410 F Cl OCH₃OCH₂(CO)OCH₂CH₃ I.a.411 F Cl OCH₃ OCH(CH₃)(CO)OCH₃ I.a.412 F Cl OCH₃OCH(CH₃)(CO)OCH₂CH₃ I.a.413 F Cl OCH₃ OCH₂-cyclopropyl I.a.414 F Cl OCH₃OCH₂-cyclobutyl I.a.415 F Cl OCH₃ SCH₃ I.a.416 F Cl OCH₃ SC₂H₅ I.a.417 FCl OCH₃ NHSO₂CH₃ I.a.418 F Cl OCH₃ NHSO₂CH(CH₃)₂ I.a.419 F Cl OCH₃NHSO₂N(CH₃)₂ I.a.420 F Cl OCH₃ NHSO₂N(CH₃)[CH(CH₃)₂] I.a.421 F CN H OHI.a.422 F CN H OCH₃ I.a.423 F CN H OC₂H₅ I.a.424 F CN H OCH(CH₃)₂I.a.425 F CN H OCH₂CH₂CH₃ I.a.426 F CN H OCH₂CH(CH₃)₂ I.a.427 F CN HOCH₂CH═CH₂ I.a.428 F CN H OCH₂C≡CH I.a.429 F CN H OCH₂CF₃ I.a.430 F CN HOCH₂CHF₂ I.a.431 F CN H OC₆H₅ I.a.432 F CN H OCH₂(C₆H₅) I.a.433 F CN HOCH₂OCH₃ I.a.434 F CN H OCH₂OCH₂CH₃ I.a.435 F CN H OCH₂CH₂OCH₃ I.a.436 FCN H OCH₂CH₂OCH₂CH₃ I.a.437 F CN H OCH₂(CO)OCH₃ I.a.438 F CN HOCH₂(CO)OCH₂CH₃ I.a.439 F CN H OCH(CH₃)(CO)OCH₃ I.a.440 F CN HOCH(CH₃)(CO)OCH₂CH₃ I.a.441 F CN H OCH₂-cyclopropyl I.a.442 F CN HOCH₂-cyclobutyl I.a.443 F CN H SCH₃ I.a.444 F CN H SC₂H₅ I.a.445 F CN HNHSO₂CH₃ I.a.446 F CN H NHSO₂CH(CH₃)₂ I.a.447 F CN H NHSO₂N(CH₃)₂I.a.448 F CN H NHSO₂N(CH₃)[CH(CH₃)₂] I.a.449 F CN CH₃ OH I.a.450 F CNCH₃ OCH₃ I.a.451 F CN CH₃ OC₂H₅ I.a.452 F CN CH₃ OCH(CH₃)₂ I.a.453 F CNCH₃ OCH₂CH₂CH₃ I.a.454 F CN CH₃ OCH₂CH(CH₃)₂ I.a.455 F CN CH₃ OCH₂CH═CH₂I.a.456 F CN CH₃ OCH₂C≡CH I.a.457 F CN CH₃ OCH₂CF₃ I.a.458 F CN CH₃OCH₂CHF₂ I.a.459 F CN CH₃ OC₆H₅ I.a.460 F CN CH₃ OCH₂(C₆H₅) I.a.461 F CNCH₃ OCH₂OCH₃ I.a.462 F CN CH₃ OCH₂OCH₂CH₃ I.a.463 F CN CH₃ OCH₂CH₂OCH₃I.a.464 F CN CH₃ OCH₂CH₂OCH₂CH₃ I.a.465 F CN CH₃ OCH₂(CO)OCH₃ I.a.466 FCN CH₃ OCH₂(CO)OCH₂CH₃ I.a.467 F CN CH₃ OCH(CH₃)(CO)OCH₃ I.a.468 F CNCH₃ OCH(CH₃)(CO)OCH₂CH₃ I.a.469 F CN CH₃ OCH₂-cyclopropyl I.a.470 F CNCH₃ OCH₂-cyclobutyl I.a.471 F CN CH₃ SCH₃ I.a.472 F CN CH₃ SC₂H₅ I.a.473F CN CH₃ NHSO₂CH₃ I.a.474 F CN CH₃ NHSO₂CH(CH₃)₂ I.a.475 F CN CH₃NHSO₂N(CH₃)₂ I.a.476 F CN CH₃ NHSO₂N(CH₃)[CH(CH₃)₂] I.a.477 F CN OCH₃ OHI.a.478 F CN OCH₃ OCH₃ I.a.479 F CN OCH₃ OC₂H₅ I.a.480 F CN OCH₃OCH(CH₃)₂ I.a.481 F CN OCH₃ OCH₂CH₂CH₃ I.a.482 F CN OCH₃ OCH₂CH(CH₃)₂I.a.483 F CN OCH₃ OCH₂CH═CH₂ I.a.484 F CN OCH₃ OCH₂C≡CH I.a.485 F CNOCH₃ OCH₂CF₃ I.a.486 F CN OCH₃ OCH₂CHF₂ I.a.487 F CN OCH₃ OC₆H₅ I.a.488F CN OCH₃ OCH₂(C₆H₅) I.a.489 F CN OCH₃ OCH₂OCH₃ I.a.490 F CN OCH₃OCH₂OCH₂CH₃ I.a.491 F CN OCH₃ OCH₂CH₂OCH₃ I.a.492 F CN OCH₃OCH₂CH₂OCH₂CH₃ I.a.493 F CN OCH₃ OCH₂(CO)OCH₃ I.a.494 F CN OCH₃OCH₂(CO)OCH₂CH₃ I.a.495 F CN OCH₃ OCH(CH₃)(CO)OCH₃ I.a.496 F CN OCH₃OCH(CH₃)(CO)OCH₂CH₃ I.a.497 F CN OCH₃ OCH₂-cyclopropyl I.a.498 F CN OCH₃OCH₂-cyclobutyl I.a.499 F CN OCH₃ SCH₃ I.a.500 F CN OCH₃ SC₂H₅ I.a.501 FCN OCH₃ NHSO₂CH₃ I.a.502 F CN OCH₃ NHSO₂CH(CH₃)₂ I.a.503 F CN OCH₃NHSO₂N(CH₃)₂ I.a.504 F CN OCH₃ NHSO₂N(CH₃)[CH(CH₃)₂] I.a.505 H Br H OHI.a.506 H Br H OCH₃ I.a.507 H Br H OC₂H₅ I.a.508 H Br H OCH(CH₃)₂I.a.509 H Br H OCH₂CH₂CH₃ I.a.510 H Br H OCH₂CH(CH₃)₂ I.a.511 H Br HOCH₂CH═CH₂ I.a.512 H Br H OCH₂C≡CH I.a.513 H Br H OCH₂CF₃ I.a.514 H Br HOCH₂CHF₂ I.a.515 H Br H OC₆H₅ I.a.516 H Br H OCH₂(C₆H₅) I.a.517 H Br HOCH₂OCH₃ I.a.518 H Br H OCH₂OCH₂CH₃ I.a.519 H Br H OCH₂CH₂OCH₃ I.a.520 HBr H OCH₂CH₂OCH₂CH₃ I.a.521 H Br H OCH₂(CO)OCH₃ I.a.522 H Br HOCH₂(CO)OCH₂CH₃ I.a.523 H Br H OCH(CH₃)(CO)OCH₃ I.a.524 H Br HOCH(CH₃)(CO)OCH₂CH₃ I.a.525 H Br H OCH₂-cyclopropyl I.a.526 H Br HOCH₂-cyclobutyl I.a.527 H Br H SCH₃ I.a.528 H Br H SC₂H₅ I.a.529 H Br HNHSO₂CH₃ I.a.530 H Br H NHSO₂CH(CH₃)₂ I.a.531 H Br H NHSO₂N(CH₃)₂I.a.532 H Br H NHSO₂N(CH₃)[CH(CH₃)₂] I.a.533 H Br CH₃ OH I.a.534 H BrCH₃ OCH₃ I.a.535 H Br CH₃ OC₂H₅ I.a.536 H Br CH₃ OCH(CH₃)₂ I.a.537 H BrCH₃ OCH₂CH₂CH₃ I.a.538 H Br CH₃ OCH₂CH(CH₃)₂ I.a.539 H Br CH₃ OCH₂CH═CH₂I.a.540 H Br CH₃ OCH₂C≡CH I.a.541 H Br CH₃ OCH₂CF₃ I.a.542 H Br CH₃OCH₂CHF₂ I.a.543 H Br CH₃ OC₆H₅ I.a.544 H Br CH₃ OCH₂(C₆H₅) I.a.545 H BrCH₃ OCH₂OCH₃ I.a.546 H Br CH₃ OCH₂OCH₂CH₃ I.a.547 H Br CH₃ OCH₂CH₂OCH₃I.a.548 H Br CH₃ OCH₂CH₂OCH₂CH₃ I.a.549 H Br CH₃ OCH₂(CO)OCH₃ I.a.550 HBr CH₃ OCH₂(CO)OCH₂CH₃ I.a.551 H Br CH₃ OCH(CH₃)(CO)OCH₃ I.a.552 H BrCH₃ OCH(CH₃)(CO)OCH₂CH₃ I.a.553 H Br CH₃ OCH₂-cyclopropyl I.a.554 H BrCH₃ OCH₂-cyclobutyl I.a.555 H Br CH₃ SCH₃ I.a.556 H Br CH₃ SC₂H₅ I.a.557H Br CH₃ NHSO₂CH₃ I.a.558 H Br CH₃ NHSO₂CH(CH₃)₂ I.a.559 H Br CH₃NHSO₂N(CH₃)₂ I.a.560 H Br CH₃ NHSO₂N(CH₃)[CH(CH₃)₂] I.a.561 H Br OCH₃ OHI.a.562 H Br OCH₃ OCH₃ I.a.563 H Br OCH₃ OC₂H₅ I.a.564 H Br OCH₃OCH(CH₃)₂ I.a.565 H Br OCH₃ OCH₂CH₂CH₃ I.a.566 H Br OCH₃ OCH₂CH(CH₃)₂I.a.567 H Br OCH₃ OCH₂CH═CH₂ I.a.568 H Br OCH₃ OCH₂C≡CH I.a.569 H BrOCH₃ OCH₂CF₃ I.a.570 H Br OCH₃ OCH₂CHF₂ I.a.571 H Br OCH₃ OC₆H₅ I.a.572H Br OCH₃ OCH₂(C₆H₅) I.a.573 H Br OCH₃ OCH₂OCH₃ I.a.574 H Br OCH₃OCH₂OCH₂CH₃ I.a.575 H Br OCH₃ OCH₂CH₂OCH₃ I.a.576 H Br OCH₃OCH₂CH₂OCH₂CH₃ I.a.577 H Br OCH₃ OCH₂(CO)OCH₃ I.a.578 H Br OCH₃OCH₂(CO)OCH₂CH₃ I.a.579 H Br OCH₃ OCH(CH₃)(CO)OCH₃ I.a.580 H Br OCH₃OCH(CH₃)(CO)OCH₂CH₃ I.a.581 H Br OCH₃ OCH₂-cyclopropyl I.a.582 H Br OCH₃OCH₂-cyclobutyl I.a.583 H Br OCH₃ SCH₃ I.a.584 H Br OCH₃ SC₂H₅ I.a.585 HBr OCH₃ NHSO₂CH₃ I.a.586 H Br OCH₃ NHSO₂CH(CH₃)₂ I.a.587 H Br OCH₃NHSO₂N(CH₃)₂ I.a.588 H Br OCH₃ NHSO₂N(CH₃)[CH(CH₃)₂] I.a.589 F Br H OHI.a.590 F Br H OCH₃ I.a.591 F Br H OC₂H₅ I.a.592 F Br H OCH(CH₃)₂I.a.593 F Br H OCH₂CH₂CH₃ I.a.594 F Br H OCH₂CH(CH₃)₂ I.a.595 F Br HOCH₂CH═CH₂ I.a.596 F Br H OCH₂C≡CH I.a.597 F Br H OCH₂CF₃ I.a.598 F Br HOCH₂CHF₂ I.a.599 F Br H OC₆H₅ I.a.600 F Br H OCH₂(C₆H₅) I.a.601 F Br HOCH₂OCH₃ I.a.602 F Br H OCH₂OCH₂CH₃ I.a.603 F Br H OCH₂CH₂OCH₃ I.a.604 FBr H OCH₂CH₂OCH₂CH₃ I.a.605 F Br H OCH₂(CO)OCH₃ I.a.606 F Br HOCH₂(CO)OCH₂CH₃ I.a.607 F Br H OCH(CH₃)(CO)OCH₃ I.a.608 F Br HOCH(CH₃)(CO)OCH₂CH₃ I.a.609 F Br H OCH₂-cyclopropyl I.a.610 F Br HOCH₂-cyclobutyl I.a.611 F Br H SCH₃ I.a.612 F Br H SC₂H₅ I.a.613 F Br HNHSO₂CH₃ I.a.614 F Br H NHSO₂CH(CH₃)₂ I.a.615 F Br H NHSO₂N(CH₃)₂I.a.616 F Br H NHSO₂N(CH₃)[CH(CH₃)₂] I.a.617 F Br CH₃ OH I.a.618 F BrCH₃ OCH₃ I.a.619 F Br CH₃ OC₂H₅ I.a.620 F Br CH₃ OCH(CH₃)₂ I.a.621 F BrCH₃ OCH₂CH₂CH₃ I.a.622 F Br CH₃ OCH₂CH(CH₃)₂ I.a.623 F Br CH₃ OCH₂CH═CH₂I.a.624 F Br CH₃ OCH₂C≡CH I.a.625 F Br CH₃ OCH₂CF₃ I.a.626 F Br CH₃OCH₂CHF₂ I.a.627 F Br CH₃ OC₆H₅ I.a.628 F Br CH₃ OCH₂(C₆H₅) I.a.629 F BrCH₃ OCH₂OCH₃ I.a.630 F Br CH₃ OCH₂OCH₂CH₃ I.a.631 F Br CH₃ OCH₂CH₂OCH₃I.a.632 F Br CH₃ OCH₂CH₂OCH₂CH₃ I.a.633 F Br CH₃ OCH₂(CO)OCH₃ I.a.634 FBr CH₃ OCH₂(CO)OCH₂CH₃ I.a.635 F Br CH₃ OCH(CH₃)(CO)OCH₃ I.a.636 F BrCH₃ OCH(CH₃)(CO)OCH₂CH₃ I.a.637 F Br CH₃ OCH₂-cyclopropyl I.a.638 F BrCH₃ OCH₂-cyclobutyl I.a.639 F Br CH₃ SCH₃ I.a.640 F Br CH₃ SC₂H₅ I.a.641F Br CH₃ NHSO₂CH₃ I.a.642 F Br CH₃ NHSO₂CH(CH₃)₂ I.a.643 F Br CH₃NHSO₂N(CH₃)₂ I.a.644 F Br CH₃ NHSO₂N(CH₃)[CH(CH₃)₂] I.a.645 F Br OCH₃ OHI.a.646 F Br OCH₃ OCH₃ I.a.647 F Br OCH₃ OC₂H₅ I.a.648 F Br OCH₃OCH(CH₃)₂ I.a.649 F Br OCH₃ OCH₂CH₂CH₃ I.a.650 F Br OCH₃ OCH₂CH(CH₃)₂I.a.651 F Br OCH₃ OCH₂CH═CH₂ I.a.652 F Br OCH₃ OCH₂C≡CH I.a.653 F BrOCH₃ OCH₂CF₃ I.a.654 F Br OCH₃ OCH₂CHF₂ I.a.655 F Br OCH₃ OC₆H₅ I.a.656F Br OCH₃ OCH₂(C₆H₅) I.a.657 F Br OCH₃ OCH₂OCH₃ I.a.658 F Br OCH₃OCH₂OCH₂CH₃ I.a.659 F Br OCH₃ OCH₂CH₂OCH₃ I.a.660 F Br OCH₃OCH₂CH₂OCH₂CH₃ I.a.661 F Br OCH₃ OCH₂(CO)OCH₃ I.a.662 F Br OCH₃OCH₂(CO)OCH₂CH₃ I.a.663 F Br OCH₃ OCH(CH₃)(CO)OCH₃ I.a.664 F Br OCH₃OCH(CH₃)(CO)OCH₂CH₃ I.a.665 F Br OCH₃ OCH₂-cyclopropyl I.a.666 F Br OCH₃OCH₂-cyclobutyl I.a.667 F Br OCH₃ SCH₃ I.a.668 F Br OCH₃ SC₂H₅ I.a.669 FBr OCH₃ NHSO₂CH₃ I.a.670 F Br OCH₃ NHSO₂CH(CH₃)₂ I.a.671 F Br OCH₃NHSO₂N(CH₃)₂ I.a.672 F Br OCH₃ NHSO₂N(CH₃)[CH(CH₃)₂]

Also preferred are the uracilpyridines of formula (.b), preferably theuracilpyridines of formulae (I.b.1) to (I.b.672), particularly preferredthe uracilpyridines of formulae (I.b.1) to (I.b.504), which differ fromthe corresponding uracilpyridines of formulae (I.a.1) to (I.a.672) onlyin that Q is S:

Also preferred are the uracilpyridines of formula (I.c), preferably theuracilpyridines of formulae (I.c.1) to (I.c.672), particularly preferredthe uracilpyridines of formulae (I.c.1) to (I.c.504), which differ fromthe corresponding uracilpyridines of formulae (I.a.1) to (I.a.672) onlyin that Z is Z-2, wherein R^(a), R^(b), R^(d) and R^(e) are H:

Also preferred are the uracilpyridines of formula (I.d), preferably theuracilpyridines of formulae (I.d.1) to (I.d.672), particularly preferredthe uracilpyridines of formulae (I.d.1) to (I.d.504), which differ fromthe corresponding uracilpyridines of formulae (I.a.1) to (I.a.672) onlyin that Z is Z-3, wherein R^(a), R^(b), R^(d) and R^(e) are H:

Also preferred are the uracilpyridines of formula (I.e), preferably theuracilpyridines of formulae (I.e.1) to (I.e.672), particularly preferredthe uracilpyridines of formulae (I.e.1) to (I.e.504), which differ fromthe corresponding uracilpyridines of formulae (I.a.1) to (I.a.672) onlyin that Z is Z-4, wherein R^(b), R^(c) and R^(d) are H:

Also preferred are the uracilpyridines of formula (I.f), preferably theuracilpyridines of formulae (I.f.1) to (I.f.672), particularly preferredthe uracilpyridines of formulae (I.f.1) to (I.f.504), which differ fromthe corresponding uracilpyridines of formulae (I.a.1) to (I.a.672) onlyin that Z is Z-5, wherein R^(a). R^(c) and R^(d) are H:

Also preferred are the uracilpyridines of formula (I.g), preferably theuracilpyridines of formulae (I.g.1) to (I.g.672),particularly preferredthe uracilpyridines of formulae (I.g.1) to (I.g.504), which differ fromthe corresponding uracilpyridines of formulae (I.a.1) to (I.a.672) onlyin that Z is Z-6, wherein R^(a), R^(b) and R^(d) are H:

Also preferred are the uracilpyridines of formula (I.h), preferably theuracilpyridines of formulae (I.h.1) to (I.h.672), particularly preferredthe uracilpyridines of formulae (I.h.1) to (I.h.504), which differ fromthe corresponding uracilpyridines of formulae (I.a.1) to (I.a.672) onlyin that Z is Z-7, wherein R^(a), R^(b) and R^(c) are H:

Also preferred are the uracilpyridines of formula (I.i), preferably theuracilpyridines of formulae (I.i.1) to (I.i.672), particularly preferredthe uracilpyridines of formulae (I.i.1) to (I.i.504), which differ fromthe corresponding uracilpyridines of formulae (I.a.1) to (I.a.672) onlyin that Z is Z-7, wherein R^(a), R^(b) and R^(c) are H, and Q is S:

Also preferred are the uracilpyridines of formula (I.k), preferably theuracilpyridines of formulae (I.k.1) to (I.k.672), particularly preferredthe uracilpyridines of formulae (I.k.1) to (I.k.504), which differ fromthe corresponding uracilpyridines of formulae (I.a.1) to (I.a.672) onlyin that Z is Z-8, wherein R^(b), R^(c) and R^(e) are H:

Also preferred are the uracilpyridines of formula (I.l), preferably theuracilpyridines of formulae (I.l.1) to (I.l.672), particularly preferredthe uracilpyridines of formulae (I.l.1) to (I.l.504), which differ fromthe corresponding uracilpyridines of formulae (I.a.1) to (I.a.672) onlyin that Z is Z-9, wherein R^(a), R^(c) and R^(e) are H:

Also preferred are the uracilpyridines of formula (I.m), preferably theuracilpyridines of formulae (I.m.1) to (I.m.672), particularly preferredthe uracilpyridines of formulae (I.m.1) to (I.m.504), which differ fromthe corresponding uracilpyridines of formulae (I.a.1) to (I.a.672) onlyin that Z is Z-10, wherein R^(a), R^(b) and R^(e) are H:

Also preferred are the uracilpyridines of formula (I.n), preferably theuracilpyridines of formulae (I.n.1) to (I.n.672), particularly preferredthe uracilpyridines of formulae (I.n.1) to (I.n.504), which differ fromthe corresponding uracilpyridines of formulae (I.a.1) to (I.a.672) onlyin that Z is Z-11, wherein R^(a), R^(b) and R^(c) are H:

Also preferred are the uracilpyridines of formula (I.o), preferably theuracilpyridines of formulae (I.o.1) to (I.o.672), particularly preferredthe uracilpyridines of formulae (I.o.1) to (I.o.504), which differ fromthe corresponding uracilpyridines of formulae (I.a.1) to (I.a.672) onlyin that Z is Z-12, wherein R^(b), R^(d) and R^(e) are H:

Also preferred are the uracilpyridines of formula (I.p), preferably theuracilpyridines of formulae (I.p.1) to (I.p.672), particularly preferredthe uracilpyridines of formulae (I.p.1) to (I.p.504), which differ fromthe corresponding uracilpyridines of formulae (I.a.1) to (I.a.672) onlyin that Z is Z-13, wherein R^(a), R^(d) and R^(e) are H:

Also preferred are the uracilpyridines of formula (I.q), preferably theuracilpyridines of formulae (I.q.1) to (I.q.672), particularly preferredthe uracilpyridines of formulae (I.q.1) to (I.q.504), which differ fromthe corresponding uracilpyridines of formulae (I.a.1) to (I.a.672) onlyin that Z is Z-21, wherein R^(a) and R^(c) are H:

To widen the spectrum of action and to achieve synergistic effects, theuracilpyridines of formula (I) may be mixed with a large number ofrepresentatives of other herbicidal or growth-regulating activeingredient groups and then applied concomitantly. Suitable componentsfor mixtures are, for example,

herbicides from the classes of the acetamides, amides,aryloxyphenoxypropionates, benzamides, benzofuran, benzoic acids,benzothiadiazinones, bipyridylium, carbamates, chloroacetamides,chlorocarboxylic acids, cyclohexanediones, dinitroanilines,dinitrophenol, diphenyl ether, glycines, imidazolinones, isoxazoles,isoxazolidinones, nitriles, N-phenylphthalimides, oxadiazoles,oxazolidinediones, oxyacetamides, phenoxycarboxylic acids,phenylcarbamates, phenylpyrazoles, phenylpyrazolines, phenylpyridazines,phosphinic acids, phosphoroamidates, phosphorodithioates, phthalamates,pyrazoles, pyridazinones, pyridines, pyridinecarboxylic acids,pyridinecarboxamides, pyrimidinediones, pyrimidinyl(thio)benzoates,quinolinecarboxylic acids, semicarbazones,sulfonylaminocarbonyltriazolinones, sulfonylureas, tetrazolinones,thiadiazoles, thiocarbamates, triazines, triazinones, triazoles,triazolinones, triazolocarboxamides, triazolopyrimidines, triketones,uracils, ureas.

It may furthermore be beneficial to apply the uracilpyridines of formula(I) alone or in combination with other herbicides, or else in the formof a mixture with other crop protection agents, for example togetherwith agents for controlling pests or phytopathogenic fungi or bacteria.Also of interest is the miscibility with mineral salt solutions, whichare employed for treating nutritional and trace element deficiencies.Other additives such as non-phytotoxic oils and oil concentrates mayalso be added.

In one embodiment of the present invention the compositions according tothe present invention comprise at least one uracilpyridine of formula(I) (compound A) and at least one further active compound selected fromherbicides B, preferably herbicides B of class b1) to b15), and safenersC (compound C).

In another embodiment of the present invention the compositionsaccording to the present invention comprise at least one uracilpyridineof formula (I) and at least one further active compound B (herbicide B).

The further herbicidal compound B (component B) is preferably selectedfrom the herbicides of class b1) to b15):

-   -   b1) lipid biosynthesis inhibitors;    -   b2) acetolactate synthase inhibitors (ALS inhibitors);    -   b3) photosynthesis inhibitors;    -   b4) protoporphyrinogen-IX oxidase inhibitors,    -   b5) bleacher herbicides;    -   b6) enolpyruvyl shikimate 3-phosphate synthase inhibitors (EPSP        inhibitors);    -   b7) glutamine synthetase inhibitors;    -   b8) 7,8-dihydropteroate synthase inhibitors (DHP inhibitors);    -   b9) mitosis inhibitors;    -   b10) inhibitors of the synthesis of very long chain fatty acids        (VLCFA inhibitors);    -   b11) cellulose biosynthesis inhibitors;    -   b12) decoupler herbicides;    -   b13) auxinic herbicides;    -   b14) auxin transport inhibitors; and    -   b15) other herbicides selected from the group consisting of        bromobutide, chlorflurenol, chlorflurenol-methyl, cinmethylin,        cumyluron, dalapon, dazomet, difenzoquat,        difenzoquat-metilsulfate, dimethipin, DSMA, dymron, endothal and        its salts, etobenzanid, flamprop, flamprop-isopropyl,        flamprop-methyl, flamprop-M-isopropyl, flamprop-M-methyl,        flurenol, flurenol-butyl, flurprimidol, fosamine,        fosamine-ammonium, indanofan, indaziflam, maleic hydrazide,        mefluidide, metam, methiozolin (CAS 403640-27-7), methyl azide,        methyl bromide, methyl-dymron, methyl iodide, MSMA, oleic acid,        oxaziclomefone, pelargonic acid, pyributicarb, quinoclamine,        triaziflam, tridiphane and        6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinol (CAS        499223-49-3) and its salts and esters;

including their agriculturally acceptable salts or derivatives.

Preference is given to those compositions according to the presentinvention comprising at least one herbicide B selected from herbicidesof class b2, b3, b4, b5, b6, b7, b9, b10 and b13.

Specific preference is given to those compositions according to thepresent invention which comprise at least one herbicide B selected fromthe herbicides of class b4, b6, b7, b9, b10 and b13.

Particular preference is given to those compositions according to thepresent invention which comprise at least one herbicide B selected fromthe herbicides of class b4, b6, b10 and b13.

Examples of herbicides B which can be used in combination with theuracilpyridines of formula (I) of formula (I) according to the presentinvention are:

b1) from the group of the lipid biosynthesis inhibitors:

ACC-herbicides such as alloxydim, alloxydim-sodium, butroxydim,clethodim, clodinafop, clodinafop-propargyl, cycloxydim, cyhalofop,cyhalofop-butyl, diclofop, diclofop-methyl, fenoxaprop,fenoxaprop-ethyl, fenoxaprop-P, fenoxaprop-P-ethyl, fluazifop,fluazifop-butyl, fluazifop-P, fluazifop-P-butyl, haloxyfop,haloxyfop-methyl, haloxyfop-P, haloxyfop-P-methyl, metamifop, pinoxaden,profoxydim, propaquizafop, quizalofop, quizalofop-ethyl,quizalofop-tefuryl, quizalofop-P, quizalofop-P-ethyl,quizalofop-P-tefuryl, sethoxydim, tepraloxydim, tralkoxydim,

4-(4′-Chloro-4-cyclopropyl-2′-fluoro[1,1′-biphenyl]-3-yl)-5-hydroxy-2,2,6,6-tetramethyl-2H-pyran-3(6H)-one (CAS 1312337-72-6);4-(2′,4′-Dichloro-4-cyclopropyl[1,1′-biphenyl]-3-yl)-5-hydroxy-2,2,6,6-tetramethyl-2H-pyran-3(6H)-one(CAS 1312337-45-3);4-(4′-Chloro-4-ethyl-2′-fluoro[1,1′-biphenyl]-3-yl)-5-hydroxy-2,2,6,6-tetramethyl-2H-pyran-3(6H)-one(CAS 1033757-93-5);4-(2′,4′-Dichloro-4-ethyl[1,1′-biphenyl]-3-yl)-2,2,6,6-tetramethyl-2H-pyran-3,5(4H,6H)-dione(CAS 1312340-84-3);5-(Acetyloxy)-4-(4′-chloro-4-cyclopropyl-2′-fluoro[1,1′-biphenyl]-3-yl)-3,6-dihydro-2,2,6,6-tetramethyl-2H-pyran-3-one(CAS 1312337-48-6);5-(Acetyloxy)-4-(2′,4′-dichloro-4-cyclopropyl-[1,1′-biphenyl]-3-yl)-3,6-dihydro-2,2,6,6-tetramethyl-2H-pyran-3-one;5-(Acetyloxy)-4-(4′-chloro-4-ethyl-2′-fluoro[1,1′-biphenyl]-3-yl)-3,6-dihydro-2,2,6,6-tetramethyl-2H-pyran-3-one(CAS 1312340-82-1);5-(Acetyloxy)-4-(2′,4′-dichloro-4-ethyl[1,1′-biphenyl]-3-yl)-3,6-dihydro-2,2,6,6-tetramethyl-2H-pyran-3-one(CAS 1033760-55-2);4-(4′-Chloro-4-cyclopropyl-2′-fluoro[1,1′-biphenyl]-3-yl)-5,6-dihydro-2,2,6,6-tetramethyl-5-oxo-2H-pyran-3-ylcarbonic acid methyl ester (CAS 1312337-51-1);4-(2′,4′-Dichloro-4-cyclopropyl-[1,1′-biphenyl]-3-yl)-5,6-dihydro-2,2,6,6-tetramethyl-5-oxo-2H-pyran-3-ylcarbonic acid methyl ester;4-(4′-Chloro-4-ethyl-2′-fluoro[1,1′-biphenyl]-3-yl)-5,6-dihydro-2,2,6,6-tetramethyl-5-oxo-2H-pyran-3-ylcarbonic acid methyl ester (CAS 1312340-83-2);4-(2′,4′-Dichloro-4-ethyl[1,1′-biphenyl]-3-yl)-5,6-dihydro-2,2,6,6-tetramethyl-5-oxo-2H-pyran-3-ylcarbonic acid methyl ester (CAS 1033760-58-5); and non ACC herbicidessuch as benfuresate, butylate, cycloate, dalapon, dimepiperate, EPTC,esprocarb, ethofumesate, flupropanate, molinate, orbencarb, pebulate,prosulfocarb, TCA, thiobencarb, tiocarbazil, triallate and vernolate;

b2) from the group of the ALS inhibitors:

sulfonylureas such as amidosulfuron, azimsulfuron, bensulfuron,bensulfuron-methyl, chlorimuron, chlorimuron-ethyl, chlorsulfuron,cinosulfuron, cyclosulfamuron, ethametsulfuron, ethametsulfuron-methyl,ethoxysulfuron, flazasulfuron, flucetosulfuron, flupyrsulfuron,flupyrsulfuron-methyl-sodium, foramsulfuron, halosulfuron,halosulfuron-methyl, imazosulfuron, iodosulfuron,iodosulfuron-methyl-sodium, iofensulfuron, iofensulfuron-sodium,mesosulfuron, metazosulfuron, metsulfuron, metsulfuron-methyl,nicosulfuron, orthosulfamuron, oxasulfuron, primisulfuron,primisulfuron-methyl, propyrisulfuron, prosulfuron, pyrazosulfuron,pyrazosulfuron-ethyl, rimsulfuron, sulfometuron, sulfometuron-methyl,sulfosulfuron, thifensulfuron, thifensulfuron-methyl, triasulfuron,tribenuron, tribenuron-methyl, trifloxysulfuron, triflusulfuron,triflusulfuron-methyl and tritosulfuron,

imidazolinones such as imazamethabenz, imazamethabenz-methyl, imazamox,imazapic, imazapyr, imazaquin and imazethapyr, triazolopyrimidineherbicides and sulfonanilides such as cloransulam, cloransulam-methyl,diclosulam, flumetsulam, florasulam, metosulam, penoxsulam, pyrimisulfanand pyroxsulam,

pyrimidinylbenzoates such as bispyribac, bispyribac-sodium,pyribenzoxim, pyriftalid, pyriminobac, pyriminobac-methyl, pyrithiobac,pyrithiobac-sodium,4-[[[2-[(4,6-dimethoxy-2-pyrimidinyl)oxy]phenyl]methyl]amino]-benzoicacid-1-methylethyl ester (CAS 420138-41-6),4-[[[2-[(4,6-dimethoxy-2-pyrimidinyl)oxy]phenyl]methyl]amino]-benzoicacid propyl ester (CAS 420138-40-5),N-(4-bromophenyl)-2-[(4,6-dimethoxy-2-pyrimidinyl)oxy]benzenemethanamine(CAS 420138-01-8),

sulfonylaminocarbonyl-triazolinone herbicides such as flucarbazone,flucarbazone-sodium, propoxycarbazone, propoxycarbazone-sodium,thiencarbazone and thiencarbazone-methyl; and triafamone;

among these, a preferred embodiment of the invention relates to thosecompositions comprising at least one imidazolinone herbicide;

b3) from the group of the photosynthesis inhibitors:

amicarbazone, inhibitors of the photosystem II, e.g.1-(6-tert-butylpyrimidin-4-yl)-2-hydroxy-4-methoxy-3-methyl-2H-pyrrol-5-one(CAS 1654744-66-7),1-(5-tert-butylisoxazol-3-yl)-2-hydroxy-4-methoxy-3-methyl-2H-pyrrol-5-one(CAS 1637455-12-9),1-(5-tert-butylisoxazol-3-yl)-4-chloro-2-hydroxy-3-methyl-2H-pyrrol-5-one(CAS 1637453-94-1),1-(5-tert-butyl-1-methyl-pyrazol-3-yl)-4-chloro-2-hydroxy-3-methyl-2H-pyrrol-5-one(CAS 1654057-29-0),1-(5-tert-butyl-1-methyl-pyrazol-3-yl)-3-chloro-2-hydroxy-4-methyl-2H-pyrrol-5-one(CAS 1654747-80-4),4-hydroxy-1-methoxy-5-methyl-3-[4-(trifluoromethyl)-2-pyridyl]imidazolidin-2-one;(CAS 2023785-78-4),4-hydroxy-1,5-dimethyl-3-[4-(trifluoromethyl)-2-pyridyl]imidazolidin-2-one(CAS 2023785-79-5),5-ethoxy-4-hydroxy-1-methyl-3-[4-(trifluoromethyl)-2-pyridyl]imidazolidin-2-one(CAS 1701416-69-4),4-hydroxy-1-methyl-3-[4-(trifluoromethyl)-2-pyridyl]imidazolidin-2-one(CAS 1708087-22-2),4-hydroxy-1,5-dimethyl-3-[1-methyl-5-(trifluoromethyl)pyrazol-3-yl]imidazolidin-2-one(CAS 2023785-80-8),1-(5-tert-butylisoxazol-3-yl)-4-ethoxy-5-hydroxy-3-methyl-imidazolidin-2-one(CAS 1844836-64-1), triazine herbicides, including of chlorotriazine,triazinones, triazindiones, methylthiotriazines and pyridazinones suchas ametryn, atrazine, chloridazone, cyanazine, desmetryn,dimethametryn,hexazinone, metribuzin, prometon, prometryn, propazine,simazine, simetryn, terbumeton, terbuthylazin, terbutryn and trietazin,aryl urea such as chlorobromuron, chlorotoluron, chloroxuron, dimefuron,diuron, fluometuron, isoproturon, isouron, linuron, metamitron,methabenzthiazuron, metobenzuron, metoxuron, monolinuron, neburon,siduron, tebuthiuron and thiadiazuron, phenyl carbamates such asdesmedipham, karbutilat, phenmedipham, phenmedipham-ethyl, nitrileherbicides such as bromofenoxim, bromoxynil and its salts and esters,ioxynil and its salts and esters, uraciles such as bromacil, lenacil andterbacil, and bentazon and bentazon-sodium, pyridate, pyridafol,pentanochlor and propanil and inhibitors of the photosystem I such asdiquat, diquat-dibromide, paraquat, paraquat-dichloride andparaquat-dimetilsulfate. Among these, a preferred embodiment of theinvention relates to those compositions comprising at least one arylurea herbicide. Among these, likewise a preferred embodiment of theinvention relates to those compositions comprising at least one triazineherbicide. Among these, likewise a preferred embodiment of the inventionrelates to those compositions comprising at least one nitrile herbicide;

b4) from the group of the protoporphyrinogen-IX oxidase inhibitors:

acifluorfen, acifluorfen-sodium, azafenidin, bencarbazone,benzfendizone, bifenox, butafenacil, carfentrazone, carfentrazone-ethyl,chlomethoxyfen, chlorphtalim, cinidon-ethyl, fluazolate, flufenpyr,flufenpyr-ethyl, flumiclorac, flumiclorac-pentyl, flumioxazin,fluoroglycofen, fluoroglycofen-ethyl, fluthiacet, fluthiacet-methyl,fomesafen, halosafen, lactofen, oxadiargyl, oxadiazon, oxyfluorfen,pentoxazone, profluazol, pyraclonil, pyraflufen, pyraflufen-ethyl,saflufenacil, sulfentrazone, thidiazimin, tiafenacil, trifludimoxazin,ethyl[3-[2-chloro-4-fluoro-5-(1-methyl-6-trifluoromethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-3-yl)phenoxy]-2-pyridyloxy]acetate(CAS 353292-31-6; S-3100,N-ethyl-3-(2,6-dichloro-4-trifluoro-methylphenoxy)-5-methyl-1H-pyrazole-1-carboxamide(CAS 452098-92-9),N-tetrahydrofurfuryl-3-(2,6-dichloro-4-trifluoromethylphenoxy)-5-methyl-1H-pyrazole-1-carboxamide(CAS 915396-43-9),N-ethyl-3-(2-chloro-6-fluoro-4-trifluoromethylphenoxy)-5-methyl-1H-pyrazole-1-carboxamide(CAS 452099-05-7),N-tetrahydrofurfuryl-3-(2-chloro-6-fluoro-4-trifluoro-methylphenoxy)-5-methyl-1H-pyrazole-1-carboxamide(CAS 452100-03-7),3-[7-fluoro-3-oxo-4-(prop-2-ynyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl]-1,5-dimethyl-6-thioxo-[1,3,5]triazinan-2,4-dione(CAS 451484-50-7),2-(2,2,7-trifluoro-3-oxo-4-prop-2-ynyl-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-4,5,6,7-tetrahydro-isoindole-1,3-dione(CAS 1300118-96-0),1-methyl-6-trifluoromethyl-3-(2,2,7-trifluoro-3-oxo-4-prop-2-ynyl-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-1H-pyrimidine-2,4-dione(CAS 1304113-05-0), methyl(E)-4-[2-chloro-5-[4-chloro-5-(difluoromethoxy)-1H-methyl-pyrazol-3-yl]-4-fluoro-phenoxy]-3-methoxy-but-2-enoate(CAS 948893-00-3), and3-[7-chloro-5-fluoro-2-(trifluoromethyl)-1H-benzimidazol-4-yl]-1-methyl-6-(trifluoromethyl)-1H-pyrimidine-2,4-dione(CAS 212754-02-4);

b5) from the group of the bleacher herbicides:

PDS inhibitors: beflubutamid, diflufenican, fluridone, flurochloridone,flurtamone, norflurazon, picolinafen, and4-(3-trifluoromethylphenoxy)-2-(4-trifluoromethylphenyl)pyrimidine (CAS180608-33-7), HPPD inhibitors: benzobicyclon, benzofenap, bicyclopyrone,clomazone, fenquinotrione, isoxaflutole, mesotrione, oxotrione (CAS1486617-21-3), pyrasulfotole, pyrazolynate, pyrazoxyfen, sulcotrione,tefuryltrione, tembotrione, tolpyralate, topramezone, bleacher, unknowntarget: aclonifen, amitrole flumeturon and2-chloro-3-methylsulfanyl-N-(1-methyltetrazol-5-yl)-4-(trifluoromethyl)benzamide(CAS 1361139-71-0),2-(2,4-dichlorophenyl)methyl-4,4-dimethyl-3-isoxazolidone (CAS81777-95-9) and2-(2,5-dichlorophenyl)methyl-4,4-dimethyl-3-isoxazolidinone (CAS81778-66-7);

b6) from the group of the EPSP synthase inhibitors:

glyphosate,glyphosate-isopropylammonium,glyposate-potassiumandglyphosate-trimesium(sulfosate);

b7) from the group of the glutamine synthase inhibitors:

bilanaphos (bialaphos), bilanaphos-sodium, glufosinate, glufosinate-Pand glufosinate-ammonium;

b8) from the group of the DHP synthase inhibitors:

asulam;

b9) from the group of the mitosis inhibitors:

compounds of group K1: dinitroanilines such as benfluralin, butralin,dinitramine, ethalfluralin, fluchloralin, oryzalin, pendimethalin,prodiamine and trifluralin, phosphoramidates such as amiprophos,amiprophos-methyl, and butamiphos, benzoic acid herbicides such aschlorthal, chlorthal-dimethyl, pyridines such as dithiopyr andthiazopyr, benzamides such as propyzamide and tebutam; compounds ofgroup K2: carbetamide, chlorpropham, flamprop, flamprop-isopropyl,flamprop-methyl, flamprop-M-isopropyl, flamprop-M-methyl and propham;among these, compounds of group K1, in particular dinitroanilines arepreferred;

b10) from the group of the VLCFA inhibitors:

chloroacetamides such as acetochlor, alachlor, amidochlor, butachlor,dimethachlor, dimethenamid, dimethenamid-P, metazachlor, metolachlor,metolachlor-S, pethoxamid, pretilachlor, propachlor, propisochlor andthenylchlor, oxyacetanilides such as flufenacet and mefenacet,acetanilides such as diphenamid, naproanilide, napropamide andnapropamide-M, tetrazolinones such fentrazamide, and other herbicidessuch as anilofos, cafenstrole, fenoxasulfone, ipfencarbazone,piperophos, pyroxasulfone and isoxazoline compounds of the formulaeII.1, II.2, II.3, II.4, II.5, II.6, II.7, II.8 and II.9

-   -   the isoxazoline compounds of the formula (I)I are known in the        art, e.g. from WO 2006/024820, WO 2006/037945, WO 2007/071900        and WO 2007/096576;    -   among the VLCFA inhibitors, preference is given to        chloroacetamides and oxyacetamides;

b11) from the group of the cellulose biosynthesis inhibitors:

chlorthiamid, dichlobenil, flupoxam, indaziflam, isoxaben, triaziflamand 1-cyclohexyl-5-pentafluorphenyloxy-1⁴-[1,2,4,6]thiatriazin-3-ylamine(CAS 175899-01-1);

b12) from the group of the decoupler herbicides:

dinoseb, dinoterb and DNOC and its salts;

b13) from the group of the auxinic herbicides:

2,4-D and its salts and esters such as clacyfos, 2,4-DB and its saltsand esters, aminocyclopyrachlor and its salts and esters, aminopyralidand its salts such as aminopyralid-dimethylammonium,aminopyralid-tris(2-hydroxypropyl)ammonium and its esters, benazolin,benazolin-ethyl, chloramben and its salts and esters, clomeprop,clopyralid and its salts and esters, dicamba and its salts and esters,dichlorprop and its salts and esters, dichlorprop-P and its salts andesters, flopyrauxifen, fluroxypyr, fluroxypyr-butometyl,fluroxypyr-meptyl, halauxifen and its salts and esters (CAS943832-60-8); MCPA and its salts and esters, MCPA-thioethyl, MCPB andits salts and esters, mecoprop and its salts and esters, mecoprop-P andits salts and esters, picloram and its salts and esters, quinclorac,quinmerac, TBA (2,3,6) and its salts and esters, triclopyr and its saltsand esters, florpyrauxifen, florpyrauxifen-benzyl (CAS 1390661-72-9) and4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indol-6-yl)picolinic acid (CAS1629965-65-6);

b14) from the group of the auxin transport inhibitors: diflufenzopyr,diflufenzopyr-sodium, naptalam and naptalam-sodium;

b15) from the group of the other herbicides: bromobutide, chlorflurenol,chlorflurenol-methyl, cinmethylin, cumyluron, cyclopyrimorate (CAS499223-49-3) and its salts and esters, dalapon, dazomet, difenzoquat,difenzoquat-metilsulfate, dimethipin, DSMA, dymron, endothal and itssalts, etobenzanid, flurenol, flurenol-butyl, flurprimidol, fosamine,fosamine-ammonium, indanofan, maleic hydrazide, mefluidide, metam,methiozolin (CAS 403640-27-7), methyl azide, methyl bromide,methyl-dymron, methyl iodide, MSMA, oleic acid, oxaziclomefone,pelargonic acid, pyributicarb, quinoclamine and tridiphane.

Active compounds B and C having a carboxyl group can be employed in theform of the acid, in the form of an agriculturally suitable salt asmentioned above or else in the form of an agriculturally acceptablederivative in the compositions according to the invention.

In the case of dicamba, suitable salts include those, where thecounterion is an agriculturally acceptable cation. For example, suitablesalts of dicamba are dicamba-sodium, dicamba-potassium,dicamba-methylammonium, dicamba-dimethylammonium,dicamba-isopropylammonium, dicamba-diglycolamine, dicamba-olamine,dicamba-diolamine, dicamba-trolamine,dicamba-N,N-bis-(3-aminopropyl)methylamine anddicamba-diethylenetriamine. Examples of a suitable ester aredicamba-methyl and dicamba-butotyl.

Suitable salts of 2,4-D are 2,4-D-ammonium, 2,4-D-dimethylammonium,2,4-D-diethylammonium, 2,4-D-diethanolammonium (2,4-D-diolamine),2,4-D-triethanolammonium, 2,4-D-isopropylammonium,2,4-D-triisopropanolammonium, 2,4-D-heptylammonium,2,4-D-dodecylammonium, 2,4-D-tetradecylammonium, 2,4-D-triethylammonium,2,4-D-tris(2-hydroxypropyl)ammonium, 2,4-D-tris(isopropyl)ammonium,2,4-D-trolamine, 2,4-D-lithium, 2,4-D-sodium. Examples of suitableesters of 2,4-D are 2,4-D-butotyl, 2,4-D-2-butoxypropyl,2,4-D-3-butoxypropyl, 2,4-D-butyl, 2,4-D-ethyl, 2,4-D-ethylhexyl,2,4-D-isobutyl, 2,4-D-isooctyl, 2,4-D-isopropyl, 2,4-D-meptyl,2,4-D-methyl, 2,4-D-octyl, 2,4-D-pentyl, 2,4-D-propyl, 2,4-D-tefuryl andclacyfos.

Suitable salts of 2,4-DB are for example 2,4-DB-sodium, 2,4-DB-potassiumand 2,4-DB-dimethylammonium. Suitable esters of 2,4-DB are for example2,4-DB-butyl and 2,4-DB-isoctyl. Suitable salts of dichlorprop are forexample dichlorprop-sodium, dichlorprop-potassium anddichlorprop-dimethylammonium. Examples of suitable esters of dichlorpropare dichlorprop-butotyl and dichlorprop-isoctyl.

Suitable salts and esters of MCPA include MCPA-butotyl, MCPA-butyl,MCPA-dimethylammonium, MCPA-diolamine, MCPA-ethyl, MCPA-thioethyl,MCPA-2-ethylhexyl, MCPA-isobutyl, MCPA-isoctyl, MCPA-isopropyl,MCPA-isopropylammonium, MCPA-methyl, MCPA-olamine, MCPA-potassium,MCPA-sodium and MCPA-trolamine.

A suitable salt of MCPB is MCPB sodium. A suitable ester of MCPB isMCPB-ethyl. Suitable salts of clopyralid are clopyralid-potassium,clopyralid-olamine and clopyralid-tris-(2-hydroxypropyl)ammonium.Example of suitable esters of clopyralid is clopyralid-methyl. Examplesof a suitable ester of fluroxypyr are fluroxypyr-meptyl andfluroxypyr-2-butoxy-1-methylethyl, wherein fluroxypyr-meptyl ispreferred.

Suitable salts of picloram are picloram-dimethylammonium,picloram-potassium, picloram-triisopropanolammonium,picloram-triisopropylammonium and picloram-trolamine. A suitable esterof picloram is picloram-isoctyl.

A suitable salt of triclopyr is triclopyr-triethylammonium. Suitableesters of triclopyr are for example triclopyr-ethyl andtriclopyr-butotyl.

Suitable salts and esters of chloramben include chloramben-ammonium,chloramben-diolamine, chloramben-methyl, chloramben-methylammonium andchloramben-sodium. Suitable salts and esters of 2,3,6-TBA include2,3,6-TBA-dimethylammonium, 2,3,6-TBA-lithium, 2,3,6-TBA-potassium and2,3,6-TBA-sodium.

Suitable salts and esters of aminopyralid includeaminopyralid-potassium, aminopyralid-dimethylammonium, andaminopyralid-tris(2-hydroxypropyl)ammonium.

Suitable salts of glyphosate are for example glyphosate-ammonium,glyphosate-diammonium, glyphoste-dimethylammonium,glyphosate-isopropylammonium, glyphosate-potassium, glyphosate-sodium,glyphosate-trimesium as well as the ethanolamine and diethanolaminesalts, preferably glyphosate-diammonium, glyphosate-isopropylammoniumand glyphosate-trimesium (sulfosate).

A suitable salt of glufosinate is for example glufosinate-ammonium.

A suitable salt of glufosinate-P is for example glufosinate-P-ammonium.

Suitable salts and esters of bromoxynil are for examplebromoxynil-butyrate, bromoxynil-heptanoate, bromoxynil-octanoate,bromoxynil-potassium and bromoxynil-sodium.

Suitable salts and esters of ioxonil are for example ioxonil-octanoate,ioxonil-potassium and ioxonil-sodium.

Suitable salts and esters of mecoprop include mecoprop-butotyl,mecoprop-dimethylammonium, mecoprop-diolamine, mecoprop-ethadyl,mecoprop-2-ethylhexyl, mecoprop-isoctyl, mecoprop-methyl,mecoprop-potassium, mecoprop-sodium and mecoprop-trolamine.

Suitable salts of mecoprop-P are for example mecoprop-P-butotyl,mecoprop-P-dimethylammonium, mecoprop-P-2-ethylhexyl,mecoprop-P-isobutyl, mecoprop-P-potassium and mecoprop-P-sodium.

A suitable salt of diflufenzopyr is for example diflufenzopyr-sodium.

A suitable salt of naptalam is for example naptalam-sodium.

Suitable salts and esters of aminocyclopyrachlor are for exampleaminocyclopyrachlor-dimethylammonium, aminocyclopyrachlor-methyl,aminocyclopyrachlor-triisopropanolammonium, aminocyclopyrachlor-sodiumand aminocyclopyrachlor-potassium.

A suitable salt of quinclorac is for examplequinclorac-dimethylammonium.

A suitable salt of quinmerac is for example quinmerac-dimethylammonium.

A suitable salt of imazamox is for example imazamox-ammonium.

Suitable salts of imazapic are for example imazapic-ammonium andimazapic-isopropylammonium.

Suitable salts of imazapyr are for example imazapyr-ammonium andimazapyr-isopropylammonium.

A suitable salt of imazaquin is for example imazaquin-ammonium.

Suitable salts of imazethapyr are for example imazethapyr-ammonium andimazethapyr-isopropylammonium.

A suitable salt of topramezone is for example topramezone-sodium.

Particularly preferred herbicides Bare the herbicides Bas defined above;in particular the herbicides B.1-B.202, especially the herbicidesB.1-B.201 listed below in table B:

TABLE B Herbicide B A. 1 clethodim A. 2 clodinafop-propargyl A. 3cycloxydim A. 4 cyhalofop-butyl A. 5 fenoxaprop-ethyl A. 6fenoxaprop-P-ethyl A. 7 metamifop A. 8 pinoxaden A. 9 profoxydim A. 10sethoxydim A. 11 tepraloxydim A. 12 tralkoxydim A. 13 esprocarb A. 14ethofumesate A. 15 molinate A. 16 prosulfocarb A. 17 thiobencarb A. 18triallate A. 19 bensulfuron-methyl A. 20 bispyribac-sodium A. 21cloransulam-methyl A. 22 chlorsulfuron A. 23 clorimuron A. 24cyclosulfamuron A. 25 diclosulam A. 26 florasulam A. 27 flumetsulam A.28 flupyrsulfuron-methyl- sodium A. 29 foramsulfuron A. 30 imazamox A.31 imazamox-ammonium A. 32 imazapic A. 33 imazapic-ammonium A. 34imazapic- isopropylammonium A. 35 imazapyr A. 36 imazapyr-ammonium A. 37imazapyr- isopropylammonium A. 38 imazaquin A. 39 imazaquin-ammonium A.40 imazethapyr A. 41 imazethapyr-ammonium A. 42 imazethapyr-isopropylammonium A. 43 imazosulfuron A. 44 iodosulfuron-methyl- sodiumA. 45 iofensulfuron A. 46 iofensulfuron-sodium A. 47 mesosulfuron-methylA. 48 metazosulfuron A. 49 metsulfuron-methyl A. 50 metosulam A. 51nicosulfuron A. 52 penoxsulam A. 53 propoxycarbazon-sodium A. 54pyrazosulfuron-ethyl A. 55 pyribenzoxim A. 56 pyriftalid A. 57pyroxsulam A. 58 propyrisulfuron A. 59 rimsulfuron A. 60 sulfosulfuronA. 61 thiencarbazone-methyl A. 62 thifensulfuron-methyl A. 63tribenuron-methyl A. 64 tritosulfuron A. 65 triafamone A. 66 ametryne A.67 atrazine A. 68 bentazon A. 69 bromoxynil A. 70 bromoxynil-octanoateA. 71 bromoxynil-heptanoate A. 72 bromoxynil-potassium A. 73 diuron A.74 fluometuron A. 75 hexazinone A. 76 isoproturon A. 77 linuron A. 78metamitron A. 79 metribuzin A. 80 propanil A. 81 simazin A. 82terbuthylazine A. 83 terbutryn A. 84 paraquat-dichloride A. 85acifluorfen A. 86 butafenacil A. 87 carfentrazone-ethyl A. 88flumioxazin A. 89 fomesafen A. 90 oxadiargyl A. 91 oxyfluorfen A. 92pyraflufen A. 93 pyraflufen-ethyl A. 94 saflufenacil A. 95 sulfentrazoneA. 96 trifludimoxazin A. 97 ethyl [3-[2-chloro-4-fluoro- 5-(1-methyl-6-trifluoromethyl-2,4-dioxo- 1,2,3,4-tetrahydropyri-midin-3-yl)phenoxy]-2- pyridyloxy]acetate (CAS 353292-31-6 A. 98benzobicyclon A. 99 bicyclopyrone A. 100 clomazone A. 101 diflufenicanA. 102 flurochloridone A. 103 isoxaflutole A. 104 mesotrione A. 105norflurazone A. 106 picolinafen A. 107 sulcotrione A. 108 tefuryltrioneA. 109 tembotrione A. 110 tolpyralate A. 111 topramezone A. 112topramezone-sodium A. 113 amitrole A. 114 fluometuron A. 115fenquinotrione A. 116 glyphosate A. 117 glyphosate-ammonium A. 118glyphosate- dimethylammonium A. 119 glyphosate- isopropylammonium A. 120glyphosate-trimesium (sulfosate) A. 121 glyphosate-potassium A. 122glufosinate A. 123 glufosinate-ammonium A. 124 glufosinate-P A. 125glufosinate-P-ammonium A. 126 pendimethalin A. 127 trifluralin A. 128acetochlor A. 129 butachlor A. 130 cafenstrole A. 131 dimethenamid-P A.132 fentrazamide A. 133 flufenacet A. 134 mefenacet A. 135 metazachlorA. 136 metolachlor A. 137 S-metolachlor A. 138 pretilachlor A. 139fenoxasulfone A. 140 indaziflam A. 141 isoxaben A. 142 triaziflam A. 143ipfencarbazone A. 144 pyroxasulfone A. 145 2,4-D A. 146 2,4-D-isobutylA. 147 2,4-D-dimethylammonium A. 148 2,4-D-N,N,N-trimethylethanolammonium A. 149 aminopyralid A. 150 aminopyralid-methylA. 151 aminopyralid-dimethyl- ammonium A. 152 aminopyralid-tris(2-hydroxypropyl)ammonium A. 153 clopyralid A. 154 clopyralid-methyl A. 155clopyralid-olamine A. 156 dicamba A. 157 dicamba-butotyl A. 158dicamba-diglycolamine A. 159 dicamba- dimethylammonium A. 160dicamba-diolamine A. 161 dicamba- isopropylammonium A. 162dicamba-potassium A. 163 dicamba-sodium A. 164 dicamba-trolamine A. 165dicamba-N,N-bis-(3- aminopropyl)methylamine A. 166 dicamba-diethylenetriamine A. 167 fluroxypyr A. 168 fluroxypyr-meptyl A. 169halauxifen A. 170 halauxifen-methyl A. 171 MCPA A. 172 MCPA-2-ethylhexylA. 173 MCPA-dimethylammonium A. 174 quinclorac A. 175 quinclorac-dimethylammonium A. 176 quinmerac A. 177 quinmerac- dimethylammonium A.178 florpyrauxifen A. 179 florpyrauxifen-benzyl (CAS 1390661-72-9) A.180 aminocyclopyrachlor A. 181 aminocyclopyrachlor- potassium A. 182aminocyclopyrachlor- methyl A. 183 diflufenzopyr A. 184diflufenzopyr-sodium A. 185 dymron A. 186 indanofan A. 187oxaziclomefone A. 188 II.1 A. 189 II.2 A. 190 II.3 A. 191 II.4 A. 192II.5 A. 193 II.6 A. 194 II.7 A. 195 II.8 A. 196 II.9 A. 1974-amino-3-chloro-5-fluoro- 6-(7-fluoro-1H-indol-6- yl)picolinic acid(CAS 1629965-65-6) A. 198 flopyrauxifen A. 199 oxotrione (CAS 1486617-21-3) A. 200 cinmethylin A. 201 2-chloro-3-methylsulfanyl-N-(1-methyltetrazol-5-yl)-4- (trifluoromethyl)benzamide (CAS1361139-71-0) A. 202 2-(2,4-dichlorophenyl)- methyl-4,4-dimethyl-3-isoxazolidone (CAS 81777-95-9)

Moreover, it may be useful to apply the uracilpyridines of formula (I)in combination with safeners. Safeners are chemical compounds whichprevent or reduce damage on useful plants without having a major impacton the herbicidal action of the uracilpyridines of formula (I) towardsunwanted plants. They can be applied either before sowings (e.g. on seedtreatments, shoots or seedlings) or in the pre-emergence application orpost-emergence application of the useful plant. The safeners and theuracilpyridines of formula (I) and optionally the herbicides B can beapplied simultaneously or in succession.

In another embodiment of the present invention the compositionsaccording to the present invention comprise at least one uracilpyridineof formula (I) and at least one safener C (component C).

Suitable safeners are e.g. (quinolin-8-oxy)acetic acids,1-phenyl-5-haloalkyl-1H-1,2,4-triazol-3-carboxylic acids,1-phenyl-4,5-dihydro-5-alkyl-1H-pyrazol-3,5-dicarboxylic acids,4,5-dihydro-5,5-diaryl-3-isoxazol carboxylic acids, dichloroacetamides,alpha-oximinophenylacetonitriles, acetophenonoximes,4,6-dihalo-2-phenylpyrimidines,N-[[4-(aminocarbonyl)phenyl]sulfonyl]-2-benzoic amides, 1,8-naphthalicanhydride, 2-halo-4-(haloalkyl)-5-thiazol carboxylic acids,phosphorthiolates and N-alkyl-O-phenylcarbamates and theiragriculturally acceptable salts and their agriculturally acceptablederivatives such amides, esters, and thioesters, provided they have anacid group.

Examples of preferred safeners C are benoxacor, cloquintocet,cyometrinil, cyprosulfamide, dichlormid, dicyclonon, dietholate,fenchlorazole, fenclorim, flurazole, fluxofenim, furilazole, isoxadifen,mefenpyr, mephenate, naphthalic anhydride, oxabetrinil,4-(dichloroacetyl)-1-oxa-4-azaspiro[4.5]decane (MON4660, CAS71526-07-3), 2,2,5-trimethyl-3-(dichloroacetyl)-1,3-oxazolidine(R-29148, CAS 52836-31-4), metcamifen and BPCMS (CAS 54091-06-4);

especially preferred benoxacor, cloquintocet, cyometrinil,cyprosulfamide, dichlormid, dicyclonon, dietholate, fenchlorazole,fenclorim, flurazole, fluxofenim, furilazole, isoxadifen, mefenpyr,mephenate, naphthalic anhydride, oxabetrinil,4-(dichloroacetyl)-1-oxa-4-azaspiro[4.5]decane (MON4660, CAS71526-07-3), 2,2,5-trimethyl-3-(dichloroacetyl)-1,3-oxazolidine(R-29148, CAS 52836-31-4) and metcamifen.

Particularly preferred safeners C, which, as component C, areconstituent of the composition according to the invention are thesafeners C as defined above; in particular the safeners C.1-C.17 listedbelow in table C:

TABLE C Safener C C. 1 benoxacor C. 2 cloquintocet C. 3cloquintocet-mexyl C. 4 cyprosulfamide C. 5 dichlormid C. 6fenchlorazole C. 7 fenchlorazole-ethyl C. 8 fenclorim C. 9 furilazole C.10 isoxadifen C. 11 isoxadifen-ethyl C. 12 mefenpyr C. 13mefenpyr-diethyl C. 14 naphtalic acid anhydride C. 154-(dichloroacetyl)-1-oxa-4-azaspiro[4.5]decane (CAS 71526-07-3) C. 162,2,5-trimethyl-3-(dichloroacetyl)-1,3-oxazolidine (CAS 52836-31-4) C.17 metcamifen

The active compounds B of groups b1) to b15) and the active compounds Care known herbicides and safeners, see, for example, The Compendium ofPesticide Common Names (http://www.alanwood.net/pesticides/); FarmChemicals Handbook 2000 volume 86, Meister Publishing Company, 2000; B.Hock, C. Fedtke, R. R. Schmidt, Herbizide [Herbicides], Georg ThiemeVerlag, Stuttgart 1995; W. H. Ahrens, Herbicide Handbook, 7th edition,Weed Science Society of America, 1994; and K. K. Hatzios, HerbicideHandbook, Supplement for the 7th edition, Weed Science Society ofAmerica, 1998. 2,2,5-Trimethyl-3-(dichloroacetyl)-1,3-oxazolidine [CASNo. 52836-31-4] is also referred to as R-29148.4-(Dichloroacetyl)-1-oxa-4-azaspiro[4.5]decane [CAS No. 71526-07-3] isalso referred to as AD-67 and MON 4660.

The assignment of the active compounds to the respective mechanisms ofaction is based on current knowledge. If several mechanisms of actionapply to one active compound, this substance was only assigned to onemechanism of action.

According to a preferred embodiment of the invention, the compositioncomprises as herbicidal active compound B or component B at least one,preferably exactly one herbicide B.

According to another preferred embodiment of the invention, thecomposition comprises as herbicidal active compounds B or component B atleast two, preferably exactly two herbicides B different from eachother.

According to another preferred embodiment of the invention, thecomposition comprises as herbicidal active compounds B or component B atleast three, preferably exactly three herbicides B different from eachother.

According to another preferred embodiment of the invention, thecomposition comprises as herbicidal active compounds B or component B atleast four, preferably exactly four herbicides B different from eachother.

According to another preferred embodiment of the invention, thecomposition comprises as safening component C or component C at leastone, preferably exactly one safener C.

According to another preferred embodiment of the invention, thecomposition comprises as component B at least one, preferably exactlyone herbicide B, and as component C at least one, preferably exactlyone, safener C.

According to another preferred embodiment of the invention, thecomposition comprises at least two, preferably exactly two, herbicides Bdifferent from each other, and as component C at least one, preferablyexactly one, safener C.

According to another preferred embodiment of the invention, thecomposition comprises at least three, preferably exactly three,herbicides B different from each other, and as component C at least one,preferably exactly one, safener C.

According to another preferred embodiment of the invention, thecomposition comprises as component A at least one, preferably exactlyone compound of formula (I), preferably of formula (I.a) or (I.h), andas component B at least one, preferably exactly one, herbicide B.

According to another preferred embodiment of the invention, thecomposition comprises as component A at least one, preferably exactlyone compound of formula (I), preferably of formula (I.a) or (I.h), andat least two, preferably exactly two, herbicides B different from eachother.

According to another preferred embodiment of the invention, thecomposition comprises as component A at least one, preferably exactlyone compound of formula (I), preferably of formula (I.a) or (I.h), andat least three, preferably exactly three, herbicides B different fromeach other.

According to another preferred embodiment of the invention, thecomposition comprises as component A at least one, preferably exactlyone compound of formula (I), preferably of formula (I.a) or (I.h), andat least four, preferably exactly four, herbicides B different from eachother.

According to another preferred embodiment of the invention, thecomposition comprises as component A at least one, preferably exactlyone compound of formula (I), preferably of formula (I.a) or (I.h), andas component C at least one, preferably exactly one, safener C.

According to another preferred embodiment of the invention, thecomposition comprises as component A at least one, preferably exactlyone compound of formula (I), preferably of formula (I.a) or (I.h), ascomponent B at least one, preferably exactly one, herbicide B, and ascomponent C at least one, preferably exactly one safener C.

According to another preferred embodiment of the invention, thecomposition comprises as component A at least one, preferably exactlyone compound of formula (I), preferably of formula (I.a) or (I.h), atleast two, preferably exactly two herbicides B different from eachother, and as component C at least one, preferably exactly one, safenerC.

According to another preferred embodiment of the invention, thecomposition comprises as component A at least one, preferably exactlyone compound of formula (I), preferably of formula (I.a) or (I.h), atleast three, preferably exactly three herbicides B different from eachother, and as component C at least one, preferably exactly one, safenerC.

According to another preferred embodiment of the invention, thecomposition comprises, in addition to an uracilpyridine of formula (a),especially an active compound from the group consisting of (I.a.87),(I.a.109), (I.a.115), (I.a.255), (I.a.277), (I.a.283), (I.a.339),(I.a.361), (I.a.367), (I.h.87), (I.h.109), (I.h.115), (I.h.255),(I.h.277), (I.h.283), (I.h.339), (I.h.361) and (I.h.367),at least oneand especially exactly one herbicidally active compound from group b4),in particular selected from the group consisting of acifluorfen,butafencil, carfenetrazone-ethyl, flumioxazin, fomesafen, oxadiargyl,oxyfluorfen, pyraflufen, pyraflufen-ethyl, saflufenacil, sulfentrazone,trifludimoxazin, ethyl[3-[2-chloro-4-fluoro-5-(1-methyl-6-trifluoromethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-3-yl)phenoxy]-2-pyridloxy]acetate(CAS 353292-31-6). According to another preferred embodiment of theinvention, the composition comprises, in addition to an uracilpyridineof formula (I), especially an active compound from the group consistingof (I.a.87), (I.a.109), (I.a.115), (I.a.255), (I.a.277), (I.a.283),(I.a.339), (I.a.361), (I.a.367), (I.h.87), (I.h.109), (I.h.115),(I.h.255), (I.h.277), (I.h.283), (I.h.339), (I.h.361) and (I.h.367), atleast one and especially exactly one herbicidally active compound fromgroup b6), in particular selected from the group consisting ofglyphosate, glyphosate-ammonium, glyphosate-dimethylammonium,glyphosate-isopropylammonium and glyphosate-trimesium (sulfosate) andglyphosate-potassium.

According to another preferred embodiment of the invention, thecomposition comprises, in addition to an uracilpyridine of formula (I),especially an active compound from the group consisting of (I.a.87),(I.a.109), (I.a.115), (I.a.255), (I.a.277), (I.a.283), (I.a.339),(I.a.361), (I.a.367), (I.h.87), (I.h.109), (I.h.115), (I.h.255),(I.h.277), (I.h.283), (I.h.339), (I.h.361) and (I.h.367), at least oneand especially exactly one herbicidally active compound from group b10),in particular selected from the group consisting of acetochlor,butachlor, cafenstrole, dimethenamid-P, fentrazamide, flufenacet,mefenacet, metazachlor, metolachlor, S-metolachlor, fenoxasulfone,ipfencarbazone and pyroxasulfone. Likewise, preference is given tocompositions comprising in addition to an uracilpyridine of formula (I),especially an active compound from the group consisting of (I.a.87),(I.a.109), (I.a.115), (I.a.255), (I.a.277), (I.a.283), (I.a.339),(I.a.361), (I.a.367), (I.h.87), (I.h.109), (I.h.115), (I.h.255),(I.h.277), (I.h.283), (I.h.339), (I.h.361) and (I.h.367), at least oneand especially exactly one herbicidally active compound from group b10),in particular selected from the group consisting of isoxazolinecompounds of the formulae II.1, II.2, II.3, II.4, II.5, II.6, II.7, II.8and II.9, as defined above.

According to another preferred embodiment of the invention, thecomposition comprises, in addition to an uracilpyridine of formula (I),especially an active compound from the group consisting of (I.a.87),(I.a.109), (I.a.115), (I.a.255), (I.a.277), (I.a.283), (I.a.339),(I.a.361), (I.a.367), (I.h.87), (I.h.109), (I.h.115), (I.h.255),(I.h.277), (I.h.283), (I.h.339), (I.h.361) and (I.h.367), at least oneand especially exactly one herbicidally active compound from group b13),in particular selected from the group consisting of 2,4-D,2,4-D-isobutyl, 2,4-D-dimethylammonium,2,4-D-N,N,N-trimethylethanolammonium, aminocyclopyrachlor,aminocyclopyrachlor-potassium, aminocyclopyrachlor-methyl, aminopyralid,aminopyralid-methyl, aminopyralid-dimethylammonium,aminopyralid-tris(2-hydroxypropyl)ammonium, clopyralid,clopyralid-methyl, clopyralid-olamine, dicamba, dicamba-butotyl,dicamba-diglycolamine, dicamba-dimethylammonium, dicamba-diolamine,dicamba-isopropylammonium, dicamba-potassium, dicamba-sodium,dicamba-trolamine, dicamba-N,N-bis-(3-aminopropyl)methylamine,dicamba-diethylenetriamine, flopyrauxifen, fluroxypyr,fluroxypyr-meptyl, halauxifen, halauxifen-methyl, MCPA,MCPA-2-ethylhexyl, MCPA-dimethylammonium, quinclorac,quinclorac-dimethylammonium, quinmerac, quinmerac-dimethylammonium,florpyrauxifen, florpyrauxifen-benzyl (CAS 1390661-72-9), and4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indol-6-yl)picolinic acid.

Here and below, the term “binary compositions” includes compositionscomprising one or more, for example 1, 2 or 3, active compounds of theformula (I) and either one or more, for example 1, 2 or 3, herbicides Bor one or more safeners C.

Correspondingly, the term “ternary compositions” includes compositionscomprising one or more, for example 1, 2 or 3, active compounds of theformula (I), one or more, for example 1, 2 or 3, herbicides B and one ormore, for example 1, 2 or 3, safeners C.

In binary compositions comprising at least one compound of the formula(I) as component A and at least one herbicide B, the weight ratio of theactive compounds A:B is generally in the range of from 1:1000 to 1000:1,preferably in the range of from 1:500 to 500:1, in particular in therange of from 1:250 to 250:1 and particularly preferably in the range offrom 1:125 to 125:1.

In binary compositions comprising at least one compound of the formula(I) as component A and at least one safener C, the weight ratio of theactive compounds A:C is generally in the range of from 1:1000 to 1000:1,preferably in the range of from 1:500 to 500:1, in particular in therange of from 1:250 to 250:1 and particularly preferably in the range offrom 1:75 to 75:1.

In ternary compositions comprising at least one uracilpyridine offormula (I) as component A, at least one herbicide B and at least onesafener C, the relative proportions by weight of the components A:B aregenerally in the range of from 1:1000 to 1000:1, preferably in the rangeof from 1:500 to 500:1, in particular in the range of from 1:250 to250:1 and particularly preferably in the range of from 1:125 to 125:1,the weight ratio of the components A:C is generally in the range of from1:1000 to 1000:1, preferably in the range of from 1:500 to 500:1, inparticular in the range of from 1:250 to 250:1 and particularlypreferably in the range of from 1:75 to 75:1, and the weight ratio ofthe components B:C is generally in the range of from 1:1000 to 1000:1,preferably in the range of from 1:500 to 500:1, in particular in therange of from 1:250 to 250:1 and particularly preferably in the range offrom 1:75 to 75:1. The weight ratio of components A+B to component C ispreferably in the range of from 1:500 to 500:1, in particular in therange of from 1:250 to 250:1 and particularly preferably in the range offrom 1:75 to 75:1.

The weight ratios of the individual components in the preferred mixturesmentioned below are within the limits given herein, in particular withinthe preferred limits.

Particularly preferred are the compositions mentioned below comprisingthe uracilpyridines of formula (as defined and the substance(s) asdefined in the respective row of table 1;

especially preferred comprising as only herbicidal active compounds theuracilpyridines of formula (I) as defined and the substance(s) asdefined in the respective row of table 1;

most preferably comprising as only active compounds the uracilpyridinesof formula (I) as defined and the substance(s) as defined in therespective row of table 1.

Particularly preferred are compositions 1.1 to 1.3653, especiallycompositions 1.1 to 1.3635, comprising the uracilpyridine (Ia.339) andthe substance(s) as defined in the respective row of table 1:

TABLE 1 (compositions 1.1 to 1.3635): comp. no. herbicide B safener C1.1 B.1 — 1.2 B.2 — 1.3 B.3 — 1.4 B.4 — 1.5 B.5 — 1.6 B.6 — 1.7 B.7 —1.8 B.8 — 1.9 B.9 — 1.10 B.10 — 1.11 B.11 — 1.12 B.12 — 1.13 B.13 — 1.14B.14 — 1.15 B.15 — 1.16 B.16 — 1.17 B.17 — 1.18 B.18 — 1.19 B.19 — 1.20B.20 — 1.21 B.21 — 1.22 B.22 — 1.23 B.23 — 1.24 B.24 — 1.25 B.25 — 1.26B.26 — 1.27 B.27 — 1.28 B.28 — 1.29 B.29 — 1.30 B.30 — 1.31 B.31 — 1.32B.32 — 1.33 B.33 — 1.34 B.34 — 1.35 B.35 — 1.36 B.36 — 1.37 B.37 — 1.38B.38 — 1.39 B.39 — 1.40 B.40 — 1.41 B.41 — 1.42 B.42 — 1.43 B.43 — 1.44B.44 — 1.45 B.45 — 1.46 B.46 — 1.47 B.47 — 1.48 B.48 — 1.49 B.49 — 1.50B.50 — 1.51 B.51 — 1.52 B.52 — 1.53 B.53 — 1.54 B.54 — 1.55 B.55 — 1.56B.56 — 1.57 B.57 — 1.58 B.58. — 1.59 B.59 — 1.60 B.60 — 1.61 B.61 — 1.62B.62 — 1.63 B.63 — 1.64 B.64 — 1.65 B.65 — 1.66 B.66 — 1.67 B.67 — 1.68B.68 — 1.69 B.69 — 1.70 B.70 — 1.71 B.71 — 1.72 B.72 — 1.73 B.73 — 1.74B.74 — 1.75 B.75 — 1.76 B.76 — 1.77 B.77 — 1.78 B.78 — 1.79 B.79 — 1.80B.80 — 1.81 B.81 — 1.82 B.82 — 1.83 B.83 — 1.84 B.84 — 1.85 B.85 — 1.86B.86 — 1.87 B.87 — 1.88 B.88 — 1.89 B.89 — 1.90 B.90 — 1.91 B.91 — 1.92B.92 — 1.93 B.93 — 1.94 B.94 — 1.95 B.95 — 1.96 B.96 — 1.97 B.97 — 1.98B.98 — 1.99 B.99 — 1.100 B.100 — 1.101 B.101 — 1.102 B.102 — 1.103 B.103— 1.104 B.104 — 1.105 B.105 — 1.106 B.106 — 1.107 B.107 — 1.108 B.108 —1.109 B.109 — 1.110 B.110 — 1.111 B.111 — 1.112 B.112 — 1.113 B.113 —1.114 B.114 — 1.115 B.115 — 1.116 B.116 — 1.117 B.117 — 1.118 B.118 —1.119 B.119 — 1.120 B.120 — 1.121 B.121 — 1.122 B.122 — 1.123 B.123 —1.124 B.124 — 1.125 B.125 — 1.126 B.126 — 1.127 B.127 — 1.128 B.128 —1.129 B.129 — 1.130 B.130 — 1.131 B.131 — 1.132 B.132 — 1.133 B.133 —1.134 B.134 — 1.135 B.135 — 1.136 B.136 — 1.137 B.137 — 1.138 B.138 —1.139 B.139 — 1.140 B.140 — 1.141 B.141 — 1.142 B.142 — 1.143 B.143 —1.144 B.144 — 1.145 B.145 — 1.146 B.146 — 1.147 B.147 — 1.148 B.148 —1.149 B.149 — 1.150 B.150 — 1.151 B.151 — 1.152 B.152 — 1.153 B.153 —1.154 B.154 — 1.155 B.155 — 1.156 B.156 — 1.157 B.157 — 1.158 B.158 —1.159 B.159 — 1.160 B.160 — 1.161 B.161 — 1.162 B.162 — 1.163 B.163 —1.164 B.164 — 1.165 B.165 — 1.166 B.166 — 1.167 B.167 — 1.168 B.168 —1.169 B.169 — 1.170 B.170 — 1.171 B.171 — 1.172 B.172 — 1.173 B.173 —1.174 B.174 — 1.175 B.175 — 1.176 B.176 — 1.177 B.177 — 1.178 B.178 —1.179 B.179 — 1.180 B.180 — 1.181 B.181 — 1.182 B.182 — 1.183 B.183 —1.184 B.184 — 1.185 B.185 — 1.186 B.186 — 1.187 B.187 — 1.188 B.188 —1.189 B.189 — 1.190 B.190 — 1.191 B.191 — 1.192 B.192 — 1.193 B.193 —1.194 B.194 — 1.195 B.195 — 1.196 B.196 — 1.197 B.197 — 1.198 B.198 —1.199 B.199 — 1.200 B.200 — 1.201 B.201 — 1.202 B.1 C.1 1.203 B.2 C.11.204 B.3 C.1 1.205 B.4 C.1 1.206 B.5 C.1 1.207 B.6 C.1 1.208 B.7 C.11.209 B.8 C.1 1.210 B.9 C.1 1.211 B.10 C.1 1.212 B.11 C.1 1.213 B.12 C.11.214 B.13 C.1 1.215 B.14 C.1 1.216 B.15 C.1 1.217 B.16 C.1 1.218 B.17C.1 1.219 B.18 C.1 1.220 B.19 C.1 1.221 B.20 C.1 1.222 B.21 C.1 1.223B.22 C.1 1.224 B.23 C.1 1.225 B.24 C.1 1.226 B.25 C.1 1.227 B.26 C.11.228 B.27 C.1 1.229 B.28 C.1 1.230 B.29 C.1 1.231 B.30 C.1 1.232 B.31C.1 1.233 B.32 C.1 1.234 B.33 C.1 1.235 B.34 C.1 1.236 B.35 C.1 1.237B.36 C.1 1.238 B.37 C.1 1.239 B.38 C.1 1.240 B.39 C.1 1.241 B.40 C.11.242 B.41 C.1 1.243 B.42 C.1 1.244 B.43 C.1 1.245 B.44 C.1 1.246 B.45C.1 1.247 B.46 C.1 1.248 B.47 C.1 1.249 B.48 C.1 1.250 B.49 C.1 1.251B.50 C.1 1.252 B.51 C.1 1.253 B.52 C.1 1.254 B.53 C.1 1.255 B.54 C.11.256 B.55 C.1 1.257 B.56 C.1 1.258 B.57 C.1 1.259 B.58. C.1 1.260 B.59C.1 1.261 B.60 C.1 1.262 B.61 C.1 1.263 B.62 C.1 1.264 B.63 C.1 1.265B.64 C.1 1.266 B.65 C.1 1.267 B.66 C.1 1.268 B.67 C.1 1.269 B.68 C.11.270 B.69 C.1 1.271 B.70 C.1 1.272 B.71 C.1 1.273 B.72 C.1 1.274 B.73C.1 1.275 B.74 C.1 1.276 B.75 C.1 1.277 B.76 C.1 1.278 B.77 C.1 1.279B.78 C.1 1.280 B.79 C.1 1.281 B.80 C.1 1.282 B.81 C.1 1.283 B.82 C.11.284 B.83 C.1 1.285 B.84 C.1 1.286 B.85 C.1 1.287 B.86 C.1 1.288 B.87C.1 1.289 B.88 C.1 1.290 B.89 C.1 1.291 B.90 C.1 1.292 B.91 C.1 1.293B.92 C.1 1.294 B.93 C.1 1.295 B.94 C.1 1.296 B.95 C.1 1.297 B.96 C.11.298 B.97 C.1 1.299 B.98 C.1 1.300 B.99 C.1 1.301 B.100 C.1 1.302 B.101C.1 1.303 B.102 C.1 1.304 B.103 C.1 1.305 B.104 C.1 1.306 B.105 C.11.307 B.106 C.1 1.308 B.107 C.1 1.309 B.108 C.1 1.310 B.109 C.1 1.311B.110 C.1 1.312 B.111 C.1 1.313 B.112 C.1 1.314 B.113 C.1 1.315 B.114C.1 1.316 B.115 C.1 1.317 B.116 C.1 1.318 B.117 C.1 1.319 B.118 C.11.320 B.119 C.1 1.321 B.120 C.1 1.322 B.121 C.1 1.323 B.122 C.1 1.324B.123 C.1 1.325 B.124 C.1 1.326 B.125 C.1 1.327 B.126 C.1 1.328 B.127C.1 1.329 B.128 C.1 1.330 B.129 C.1 1.331 B.130 C.1 1.332 B.131 C.11.333 B.132 C.1 1.334 B.133 C.1 1.335 B.134 C.1 1.336 B.135 C.1 1.337B.136 C.1 1.338 B.137 C.1 1.339 B.138 C.1 1.340 B.139 C.1 1.341 B.140C.1 1.342 B.141 C.1 1.343 B.142 C.1 1.344 B.143 C.1 1.345 B.144 C.11.346 B.145 C.1 1.347 B.146 C.1 1.348 B.147 C.1 1.349 B.148 C.1 1.350B.149 C.1 1.351 B.150 C.1 1.352 B.151 C.1 1.353 B.152 C.1 1.354 B.153C.1 1.355 B.154 C.1 1.356 B.155 C.1 1.357 B.156 C.1 1.358 B.157 C.11.359 B.158 C.1 1.360 B.159 C.1 1.361 B.160 C.1 1.362 B.161 C.1 1.363B.162 C.1 1.364 B.163 C.1 1.365 B.164 C.1 1.366 B.165 C.1 1.367 B.166C.1 1.368 B.167 C.1 1.369 B.168 C.1 1.370 B.169 C.1 1.371 B.170 C.11.372 B.171 C.1 1.373 B.172 C.1 1.374 B.173 C.1 1.375 B.174 C.1 1.376B.175 C.1 1.377 B.176 C.1 1.378 B.177 C.1 1.379 B.178 C.1 1.380 B.179C.1 1.381 B.180 C.1 1.382 B.181 C.1 1.383 B.182 C.1 1.384 B.183 C.11.385 B.184 C.1 1.386 B.185 C.1 1.387 B.186 C.1 1.388 B.187 C.1 1.389B.188 C.1 1.390 B.189 C.1 1.391 B.190 C.1 1.392 B.191 C.1 1.393 B.192C.1 1.394 B.193 C.1 1.395 B.194 C.1 1.396 B.195 C.1 1.397 B.196 C.11.398 B.197 C.1 1.399 B.198 C.1 1.400 B.199 C.1 1.401 B.200 C.1 1.402B.201 C.1 1.403 B.1 C.2 1.404 B.2 C.2 1.405 B.3 C.2 1.406 B.4 C.2 1.407B.5 C.2 1.408 B.6 C.2 1.409 B.7 C.2 1.410 B.8 C.2 1.411 B.9 C.2 1.412B.10 C.2 1.413 B.11 C.2 1.414 B.12 C.2 1.415 B.13 C.2 1.416 B.14 C.21.417 B.15 C.2 1.418 B.16 C.2 1.419 B.17 C.2 1.420 B.18 C.2 1.421 B.19C.2 1.422 B.20 C.2 1.423 B.21 C.2 1.424 B.22 C.2 1.425 B.23 C.2 1.426B.24 C.2 1.427 B.25 C.2 1.428 B.26 C.2 1.429 B.27 C.2 1.430 B.28 C.21.431 B.29 C.2 1.432 B.30 C.2 1.433 B.31 C.2 1.434 B.32 C.2 1.435 B.33C.2 1.436 B.34 C.2 1.437 B.35 C.2 1.438 B.36 C.2 1.439 B.37 C.2 1.440B.38 C.2 1.441 B.39 C.2 1.442 B.40 C.2 1.443 B.41 C.2 1.444 B.42 C.21.445 B.43 C.2 1.446 B.44 C.2 1.447 B.45 C.2 1.448 B.46 C.2 1.449 B.47C.2 1.450 B.48 C.2 1.451 B.49 C.2 1.452 B.50 C.2 1.453 B.51 C.2 1.454B.52 C.2 1.455 B.53 C.2 1.456 B.54 C.2 1.457 B.55 C.2 1.458 B.56 C.21.459 B.57 C.2 1.460 B.58. C.2 1.461 B.59 C.2 1.462 B.60 C.2 1.463 B.61C.2 1.464 B.62 C.2 1.465 B.63 C.2 1.466 B.64 C.2 1.467 B.65 C.2 1.468B.66 C.2 1.469 B.67 C.2 1.470 B.68 C.2 1.471 B.69 C.2 1.472 B.70 C.21.473 B.71 C.2 1.474 B.72 C.2 1.475 B.73 C.2 1.476 B.74 C.2 1.477 B.75C.2 1.478 B.76 C.2 1.479 B.77 C.2 1.480 B.78 C.2 1.481 B.79 C.2 1.482B.80 C.2 1.483 B.81 C.2 1.484 B.82 C.2 1.485 B.83 C.2 1.486 B.84 C.21.487 B.85 C.2 1.488 B.86 C.2 1.489 B.87 C.2 1.490 B.88 C.2 1.491 B.89C.2 1.492 B.90 C.2 1.493 B.91 C.2 1.494 B.92 C.2 1.495 B.93 C.2 1.496B.94 C.2 1.497 B.95 C.2 1.498 B.96 C.2 1.499 B.97 C.2 1.500 B.98 C.21.501 B.99 C.2 1.502 B.100 C.2 1.503 B.101 C.2 1.504 B.102 C.2 1.505B.103 C.2 1.506 B.104 C.2 1.507 B.105 C.2 1.508 B.106 C.2 1.509 B.107C.2 1.510 B.108 C.2 1.511 B.109 C.2 1.512 B.110 C.2 1.513 B.111 C.21.514 B.112 C.2 1.515 B.113 C.2 1.516 B.114 C.2 1.517 B.115 C.2 1.518B.116 C.2 1.519 B.117 C.2 1.520 B.118 C.2 1.521 B.119 C.2 1.522 B.120C.2 1.523 B.121 C.2 1.524 B.122 C.2 1.525 B.123 C.2 1.526 B.124 C.21.527 B.125 C.2 1.528 B.126 C.2 1.529 B.127 C.2 1.530 B.128 C.2 1.531B.129 C.2 1.532 B.130 C.2 1.533 B.131 C.2 1.534 B.132 C.2 1.535 B.133C.2 1.536 B.134 C.2 1.537 B.135 C.2 1.538 B.136 C.2 1.539 B.137 C.21.540 B.138 C.2 1.541 B.139 C.2 1.542 B.140 C.2 1.543 B.141 C.2 1.544B.142 C.2 1.545 B.143 C.2 1.546 B.144 C.2 1.547 B.145 C.2 1.548 B.146C.2 1.549 B.147 C.2 1.550 B.148 C.2 1.551 B.149 C.2 1.552 B.150 C.21.553 B.151 C.2 1.554 B.152 C.2 1.555 B.153 C.2 1.556 B.154 C.2 1.557B.155 C.2 1.558 B.156 C.2 1.559 B.157 C.2 1.560 B.158 C.2 1.561 B.159C.2 1.562 B.160 C.2 1.563 B.161 C.2 1.564 B.162 C.2 1.565 B.163 C.21.566 B.164 C.2 1.567 B.165 C.2 1.568 B.166 C.2 1.569 B.167 C.2 1.570B.168 C.2 1.571 B.169 C.2 1.572 B.170 C.2 1.573 B.171 C.2 1.574 B.172C.2 1.575 B.173 C.2 1.576 B.174 C.2 1.577 B.175 C.2 1.578 B.176 C.21.579 B.177 C.2 1.580 B.178 C.2 1.581 B.179 C.2 1.582 B.180 C.2 1.583B.181 C.2 1.584 B.182 C.2 1.585 B.183 C.2 1.586 B.184 C.2 1.587 B.185C.2 1.588 B.186 C.2 1.589 B.187 C.2 1.590 B.188 C.2 1.591 B.189 C.21.592 B.190 C.2 1.593 B.191 C.2 1.594 B.192 C.2 1.595 B.193 C.2 1.596B.194 C.2 1.597 B.195 C.2 1.598 B.196 C.2 1.599 B.197 C.2 1.600 B.198C.2 1.601 B.199 C.2 1.602 B.200 C.2 1.603 B.201 C.2 1.604 B.1 C.3 1.605B.2 C.3 1.606 B.3 C.3 1.607 B.4 C.3 1.608 B.5 C.3 1.609 B.6 C.3 1.610B.7 C.3 1.611 B.8 C.3 1.612 B.9 C.3 1.613 B.10 C.3 1.614 B.11 C.3 1.615B.12 C.3 1.616 B.13 C.3 1.617 B.14 C.3 1.618 B.15 C.3 1.619 B.16 C.31.620 B.17 C.3 1.621 B.18 C.3 1.622 B.19 C.3 1.623 B.20 C.3 1.624 B.21C.3 1.625 B.22 C.3 1.626 B.23 C.3 1.627 B.24 C.3 1.628 B.25 C.3 1.629B.26 C.3 1.630 B.27 C.3 1.631 B.28 C.3 1.632 B.29 C.3 1.633 B.30 C.31.634 B.31 C.3 1.635 B.32 C.3 1.636 B.33 C.3 1.637 B.34 C.3 1.638 B.35C.3 1.639 B.36 C.3 1.640 B.37 C.3 1.641 B.38 C.3 1.642 B.39 C.3 1.643B.40 C.3 1.644 B.41 C.3 1.645 B.42 C.3 1.646 B.43 C.3 1.647 B.44 C.31.648 B.45 C.3 1.649 B.46 C.3 1.650 B.47 C.3 1.651 B.48 C.3 1.652 B.49C.3 1.653 B.50 C.3 1.654 B.51 C.3 1.655 B.52 C.3 1.656 B.53 C.3 1.657B.54 C.3 1.658 B.55 C.3 1.659 B.56 C.3 1.660 B.57 C.3 1.661 B.58. C.31.662 B.59 C.3 1.663 B.60 C.3 1.664 B.61 C.3 1.665 B.62 C.3 1.666 B.63C.3 1.667 B.64 C.3 1.668 B.65 C.3 1.669 B.66 C.3 1.670 B.67 C.3 1.671B.68 C.3 1.672 B.69 C.3 1.673 B.70 C.3 1.674 B.71 C.3 1.675 B.72 C.31.676 B.73 C.3 1.677 B.74 C.3 1.678 B.75 C.3 1.679 B.76 C.3 1.680 B.77C.3 1.681 B.78 C.3 1.682 B.79 C.3 1.683 B.80 C.3 1.684 B.81 C.3 1.685B.82 C.3 1.686 B.83 C.3 1.687 B.84 C.3 1.688 B.85 C.3 1.689 B.86 C.31.690 B.87 C.3 1.691 B.88 C.3 1.692 B.89 C.3 1.693 B.90 C.3 1.694 B.91C.3 1.695 B.92 C.3 1.696 B.93 C.3 1.697 B.94 C.3 1.698 B.95 C.3 1.699B.96 C.3 1.700 B.97 C.3 1.701 B.98 C.3 1.702 B.99 C.3 1.703 B.100 C.31.704 B.101 C.3 1.705 B.102 C.3 1.706 B.103 C.3 1.707 B.104 C.3 1.708B.105 C.3 1.709 B.106 C.3 1.710 B.107 C.3 1.711 B.108 C.3 1.712 B.109C.3 1.713 B.110 C.3 1.714 B.111 C.3 1.715 B.112 C.3 1.716 B.113 C.31.717 B.114 C.3 1.718 B.115 C.3 1.719 B.116 C.3 1.720 B.117 C.3 1.721B.118 C.3 1.722 B.119 C.3 1.723 B.120 C.3 1.724 B.121 C.3 1.725 B.122C.3 1.726 B.123 C.3 1.727 B.124 C.3 1.728 B.125 C.3 1.729 B.126 C.31.730 B.127 C.3 1.731 B.128 C.3 1.732 B.129 C.3 1.733 B.130 C.3 1.734B.131 C.3 1.735 B.132 C.3 1.736 B.133 C.3 1.737 B.134 C.3 1.738 B.135C.3 1.739 B.136 C.3 1.740 B.137 C.3 1.741 B.138 C.3 1.742 B.139 C.31.743 B.140 C.3 1.744 B.141 C.3 1.745 B.142 C.3 1.746 B.143 C.3 1.747B.144 C.3 1.748 B.145 C.3 1.749 B.146 C.3 1.750 B.147 C.3 1.751 B.148C.3 1.752 B.149 C.3 1.753 B.150 C.3 1.754 B.151 C.3 1.755 B.152 C.31.756 B.153 C.3 1.757 B.154 C.3 1.758 B.155 C.3 1.759 B.156 C.3 1.760B.157 C.3 1.761 B.158 C.3 1.762 B.159 C.3 1.763 B.160 C.3 1.764 B.161C.3 1.765 B.162 C.3 1.766 B.163 C.3 1.767 B.164 C.3 1.768 B.165 C.31.769 B.166 C.3 1.770 B.167 C.3 1.771 B.168 C.3 1.772 B.169 C.3 1.773B.170 C.3 1.774 B.171 C.3 1.775 B.172 C.3 1.776 B.173 C.3 1.777 B.174C.3 1.778 B.175 C.3 1.779 B.176 C.3 1.780 B.177 C.3 1.781 B.178 C.31.782 B.179 C.3 1.783 B.180 C.3 1.784 B.181 C.3 1.785 B.182 C.3 1.786B.183 C.3 1.787 B.184 C.3 1.788 B.185 C.3 1.789 B.186 C.3 1.790 B.187C.3 1.791 B.188 C.3 1.792 B.189 C.3 1.793 B.190 C.3 1.794 B.191 C.31.795 B.192 C.3 1.796 B.193 C.3 1.797 B.194 C.3 1.798 B.195 C.3 1.799B.196 C.3 1.800 B.197 C.3 1.801 B.198 C.3 1.802 B.199 C.3 1.803 B.200C.3 1.804 B.201 C.3 1.805 B.1 C.4 1.806 B.2 C.4 1.807 B.3 C.4 1.808 B.4C.4 1.809 B.5 C.4 1.810 B.6 C.4 1.811 B.7 C.4 1.812 B.8 C.4 1.813 B.9C.4 1.814 B.10 C.4 1.815 B.11 C.4 1.816 B.12 C.4 1.817 B.13 C.4 1.818B.14 C.4 1.819 B.15 C.4 1.820 B.16 C.4 1.821 B.17 C.4 1.822 B.18 C.41.823 B.19 C.4 1.824 B.20 C.4 1.825 B.21 C.4 1.826 B.22 C.4 1.827 B.23C.4 1.828 B.24 C.4 1.829 B.25 C.4 1.830 B.26 C.4 1.831 B.27 C.4 1.832B.28 C.4 1.833 B.29 C.4 1.834 B.30 C.4 1.835 B.31 C.4 1.836 B.32 C.41.837 B.33 C.4 1.838 B.34 C.4 1.839 B.35 C.4 1.840 B.36 C.4 1.841 B.37C.4 1.842 B.38 C.4 1.843 B.39 C.4 1.844 B.40 C.4 1.845 B.41 C.4 1.846B.42 C.4 1.847 B.43 C.4 1.848 B.44 C.4 1.849 B.45 C.4 1.850 B.46 C.41.851 B.47 C.4 1.852 B.48 C.4 1.853 B.49 C.4 1.854 B.50 C.4 1.855 B.51C.4 1.856 B.52 C.4 1.857 B.53 C.4 1.858 B.54 C.4 1.859 B.55 C.4 1.860B.56 C.4 1.861 B.57 C.4 1.862 B.58. C.4 1.863 B.59 C.4 1.864 B.60 C.41.865 B.61 C.4 1.866 B.62 C.4 1.867 B.63 C.4 1.868 B.64 C.4 1.869 B.65C.4 1.870 B.66 C.4 1.871 B.67 C.4 1.872 B.68 C.4 1.873 B.69 C.4 1.874B.70 C.4 1.875 B.71 C.4 1.876 B.72 C.4 1.877 B.73 C.4 1.878 B.74 C.41.879 B.75 C.4 1.880 B.76 C.4 1.881 B.77 C.4 1.882 B.78 C.4 1.883 B.79C.4 1.884 B.80 C.4 1.885 B.81 C.4 1.886 B.82 C.4 1.887 B.83 C.4 1.888B.84 C.4 1.889 B.85 C.4 1.890 B.86 C.4 1.891 B.87 C.4 1.892 B.88 C.41.893 B.89 C.4 1.894 B.90 C.4 1.895 B.91 C.4 1.896 B.92 C.4 1.897 B.93C.4 1.898 B.94 C.4 1.899 B.95 C.4 1.900 B.96 C.4 1.901 B.97 C.4 1.902B.98 C.4 1.903 B.99 C.4 1.904 B.100 C.4 1.905 B.101 C.4 1.906 B.102 C.41.907 B.103 C.4 1.908 B.104 C.4 1.909 B.105 C.4 1.910 B.106 C.4 1.911B.107 C.4 1.912 B.108 C.4 1.913 B.109 C.4 1.914 B.110 C.4 1.915 B.111C.4 1.916 B.112 C.4 1.917 B.113 C.4 1.918 B.114 C.4 1.919 B.115 C.41.920 B.116 C.4 1.921 B.117 C.4 1.922 B.118 C.4 1.923 B.119 C.4 1.924B.120 C.4 1.925 B.121 C.4 1.926 B.122 C.4 1.927 B.123 C.4 1.928 B.124C.4 1.929 B.125 C.4 1.930 B.126 C.4 1.931 B.127 C.4 1.932 B.128 C.41.933 B.129 C.4 1.934 B.130 C.4 1.935 B.131 C.4 1.936 B.132 C.4 1.937B.133 C.4 1.938 B.134 C.4 1.939 B.135 C.4 1.940 B.136 C.4 1.941 B.137C.4 1.942 B.138 C.4 1.943 B.139 C.4 1.944 B.140 C.4 1.945 B.141 C.41.946 B.142 C.4 1.947 B.143 C.4 1.948 B.144 C.4 1.949 B.145 C.4 1.950B.146 C.4 1.951 B.147 C.4 1.952 B.148 C.4 1.953 B.149 C.4 1.954 B.150C.4 1.955 B.151 C.4 1.956 B.152 C.4 1.957 B.153 C.4 1.958 B.154 C.41.959 B.155 C.4 1.960 B.156 C.4 1.961 B.157 C.4 1.962 B.158 C.4 1.963B.159 C.4 1.964 B.160 C.4 1.965 B.161 C.4 1.966 B.162 C.4 1.967 B.163C.4 1.968 B.164 C.4 1.969 B.165 C.4 1.970 B.166 C.4 1.971 B.167 C.41.972 B.168 C.4 1.973 B.169 C.4 1.974 B.170 C.4 1.975 B.171 C.4 1.976B.172 C.4 1.977 B.173 C.4 1.978 B.174 C.4 1.979 B.175 C.4 1.980 B.176C.4 1.981 B.177 C.4 1.982 B.178 C.4 1.983 B.179 C.4 1.984 B.180 C.41.985 B.181 C.4 1.986 B.182 C.4 1.987 B.183 C.4 1.988 B.184 C.4 1.989B.185 C.4 1.990 B.186 C.4 1.991 B.187 C.4 1.992 B.188 C.4 1.993 B.189C.4 1.994 B.190 C.4 1.995 B.191 C.4 1.996 B.192 C.4 1.997 B.193 C.41.998 B.194 C.4 1.999 B.195 C.4 1.1000 B.196 C.4 1.1001 B.197 C.4 1.1002B.198 C.4 1.1003 B.199 C.4 1.1004 B.200 C.4 1.1005 B.201 C.4 1.1006 B.1C.5 1.1007 B.2 C.5 1.1008 B.3 C.5 1.1009 B.4 C.5 1.1010 B.5 C.5 1.1011B.6 C.5 1.1012 B.7 C.5 1.1013 B.8 C.5 1.1014 B.9 C.5 1.1015 B.10 C.51.1016 B.11 C.5 1.1017 B.12 C.5 1.1018 B.13 C.5 1.1019 B.14 C.5 1.1020B.15 C.5 1.1021 B.16 C.5 1.1022 B.17 C.5 1.1023 B.18 C.5 1.1024 B.19 C.51.1025 B.20 C.5 1.1026 B.21 C.5 1.1027 B.22 C.5 1.1028 B.23 C.5 1.1029B.24 C.5 1.1030 B.25 C.5 1.1031 B.26 C.5 1.1032 B.27 C.5 1.1033 B.28 C.51.1034 B.29 C.5 1.1035 B.30 C.5 1.1036 B.31 C.5 1.1037 B.32 C.5 1.1038B.33 C.5 1.1039 B.34 C.5 1.1040 B.35 C.5 1.1041 B.36 C.5 1.1042 B.37 C.51.1043 B.38 C.5 1.1044 B.39 C.5 1.1045 B.40 C.5 1.1046 B.41 C.5 1.1047B.42 C.5 1.1048 B.43 C.5 1.1049 B.44 C.5 1.1050 B.45 C.5 1.1051 B.46 C.51.1052 B.47 C.5 1.1053 B.48 C.5 1.1054 B.49 C.5 1.1055 B.50 C.5 1.1056B.51 C.5 1.1057 B.52 C.5 1.1058 B.53 C.5 1.1059 B.54 C.5 1.1060 B.55 C.51.1061 B.56 C.5 1.1062 B.57 C.5 1.1063 B.58. C.5 1.1064 B.59 C.5 1.1065B.60 C.5 1.1066 B.61 C.5 1.1067 B.62 C.5 1.1068 B.63 C.5 1.1069 B.64 C.51.1070 B.65 C.5 1.1071 B.66 C.5 1.1072 B.67 C.5 1.1073 B.68 C.5 1.1074B.69 C.5 1.1075 B.70 C.5 1.1076 B.71 C.5 1.1077 B.72 C.5 1.1078 B.73 C.51.1079 B.74 C.5 1.1080 B.75 C.5 1.1081 B.76 C.5 1.1082 B.77 C.5 1.1083B.78 C.5 1.1084 B.79 C.5 1.1085 B.80 C.5 1.1086 B.81 C.5 1.1087 B.82 C.51.1088 B.83 C.5 1.1089 B.84 C.5 1.1090 B.85 C.5 1.1091 B.86 C.5 1.1092B.87 C.5 1.1093 B.88 C.5 1.1094 B.89 C.5 1.1095 B.90 C.5 1.1096 B.91 C.51.1097 B.92 C.5 1.1098 B.93 C.5 1.1099 B.94 C.5 1.1100 B.95 C.5 1.1101B.96 C.5 1.1102 B.97 C.5 1.1103 B.98 C.5 1.1104 B.99 C.5 1.1105 B.100C.5 1.1106 B.101 C.5 1.1107 B.102 C.5 1.1108 B.103 C.5 1.1109 B.104 C.51.1110 B.105 C.5 1.1111 B.106 C.5 1.1112 B.107 C.5 1.1113 B.108 C.51.1114 B.109 C.5 1.1115 B.110 C.5 1.1116 B.111 C.5 1.1117 B.112 C.51.1118 B.113 C.5 1.1119 B.114 C.5 1.1120 B.115 C.5 1.1121 B.116 C.51.1122 B.117 C.5 1.1123 B.118 C.5 1.1124 B.119 C.5 1.1125 B.120 C.51.1126 B.121 C.5 1.1127 B.122 C.5 1.1128 B.123 C.5 1.1129 B.124 C.51.1130 B.125 C.5 1.1131 B.126 C.5 1.1132 B.127 C.5 1.1133 B.128 C.51.1134 B.129 C.5 1.1135 B.130 C.5 1.1136 B.131 C.5 1.1137 B.132 C.51.1138 B.133 C.5 1.1139 B.134 C.5 1.1140 B.135 C.5 1.1141 B.136 C.51.1142 B.137 C.5 1.1143 B.138 C.5 1.1144 B.139 C.5 1.1145 B.140 C.51.1146 B.141 C.5 1.1147 B.142 C.5 1.1148 B.143 C.5 1.1149 B.144 C.51.1150 B.145 C.5 1.1151 B.146 C.5 1.1152 B.147 C.5 1.1153 B.148 C.51.1154 B.149 C.5 1.1155 B.150 C.5 1.1156 B.151 C.5 1.1157 B.152 C.51.1158 B.153 C.5 1.1159 B.154 C.5 1.1160 B.155 C.5 1.1161 B.156 C.51.1162 B.157 C.5 1.1163 B.158 C.5 1.1164 B.159 C.5 1.1165 B.160 C.51.1166 B.161 C.5 1.1167 B.162 C.5 1.1168 B.163 C.5 1.1169 B.164 C.51.1170 B.165 C.5 1.1171 B.166 C.5 1.1172 B.167 C.5 1.1173 B.168 C.51.1174 B.169 C.5 1.1175 B.170 C.5 1.1176 B.171 C.5 1.1177 B.172 C.51.1178 B.173 C.5 1.1179 B.174 C.5 1.1180 B.175 C.5 1.1181 B.176 C.51.1182 B.177 C.5 1.1183 B.178 C.5 1.1184 B.179 C.5 1.1185 B.180 C.51.1186 B.181 C.5 1.1187 B.182 C.5 1.1188 B.183 C.5 1.1189 B.184 C.51.1190 B.185 C.5 1.1191 B.186 C.5 1.1192 B.187 C.5 1.1193 B.188 C.51.1194 B.189 C.5 1.1195 B.190 C.5 1.1196 B.191 C.5 1.1197 B.192 C.51.1198 B.193 C.5 1.1199 B.194 C.5 1.1200 B.195 C.5 1.1201 B.196 C.51.1202 B.197 C.5 1.1203 B.198 C.5 1.1204 B.199 C.5 1.1205 B.200 C.51.1206 B.201 C.5 1.1207 B.1 C.6 1.1208 B.2 C.6 1.1209 B.3 C.6 1.1210 B.4C.6 1.1211 B.5 C.6 1.1212 B.6 C.6 1.1213 B.7 C.6 1.1214 B.8 C.6 1.1215B.9 C.6 1.1216 B.10 C.6 1.1217 B.11 C.6 1.1218 B.12 C.6 1.1219 B.13 C.61.1220 B.14 C.6 1.1221 B.15 C.6 1.1222 B.16 C.6 1.1223 B.17 C.6 1.1224B.18 C.6 1.1225 B.19 C.6 1.1226 B.20 C.6 1.1227 B.21 C.6 1.1228 B.22 C.61.1229 B.23 C.6 1.1230 B.24 C.6 1.1231 B.25 C.6 1.1232 B.26 C.6 1.1233B.27 C.6 1.1234 B.28 C.6 1.1235 B.29 C.6 1.1236 B.30 C.6 1.1237 B.31 C.61.1238 B.32 C.6 1.1239 B.33 C.6 1.1240 B.34 C.6 1.1241 B.35 C.6 1.1242B.36 C.6 1.1243 B.37 C.6 1.1244 B.38 C.6 1.1245 B.39 C.6 1.1246 B.40 C.61.1247 B.41 C.6 1.1248 B.42 C.6 1.1249 B.43 C.6 1.1250 B.44 C.6 1.1251B.45 C.6 1.1252 B.46 C.6 1.1253 B.47 C.6 1.1254 B.48 C.6 1.1255 B.49 C.61.1256 B.50 C.6 1.1257 B.51 C.6 1.1258 B.52 C.6 1.1259 B.53 C.6 1.1260B.54 C.6 1.1261 B.55 C.6 1.1262 B.56 C.6 1.1263 B.57 C.6 1.1264 B.58.C.6 1.1265 B.59 C.6 1.1266 B.60 C.6 1.1267 B.61 C.6 1.1268 B.62 C.61.1269 B.63 C.6 1.1270 B.64 C.6 1.1271 B.65 C.6 1.1272 B.66 C.6 1.1273B.67 C.6 1.1274 B.68 C.6 1.1275 B.69 C.6 1.1276 B.70 C.6 1.1277 B.71 C.61.1278 B.72 C.6 1.1279 B.73 C.6 1.1280 B.74 C.6 1.1281 B.75 C.6 1.1282B.76 C.6 1.1283 B.77 C.6 1.1284 B.78 C.6 1.1285 B.79 C.6 1.1286 B.80 C.61.1287 B.81 C.6 1.1288 B.82 C.6 1.1289 B.83 C.6 1.1290 B.84 C.6 1.1291B.85 C.6 1.1292 B.86 C.6 1.1293 B.87 C.6 1.1294 B.88 C.6 1.1295 B.89 C.61.1296 B.90 C.6 1.1297 B.91 C.6 1.1298 B.92 C.6 1.1299 B.93 C.6 1.1300B.94 C.6 1.1301 B.95 C.6 1.1302 B.96 C.6 1.1303 B.97 C.6 1.1304 B.98 C.61.1305 B.99 C.6 1.1306 B.100 C.6 1.1307 B.101 C.6 1.1308 B.102 C.61.1309 B.103 C.6 1.1310 B.104 C.6 1.1311 B.105 C.6 1.1312 B.106 C.61.1313 B.107 C.6 1.1314 B.108 C.6 1.1315 B.109 C.6 1.1316 B.110 C.61.1317 B.111 C.6 1.1318 B.112 C.6 1.1319 B.113 C.6 1.1320 B.114 C.61.1321 B.115 C.6 1.1322 B.116 C.6 1.1323 B.117 C.6 1.1324 B.118 C.61.1325 B.119 C.6 1.1326 B.120 C.6 1.1327 B.121 C.6 1.1328 B.122 C.61.1329 B.123 C.6 1.1330 B.124 C.6 1.1331 B.125 C.6 1.1332 B.126 C.61.1333 B.127 C.6 1.1334 B.128 C.6 1.1335 B.129 C.6 1.1336 B.130 C.61.1337 B.131 C.6 1.1338 B.132 C.6 1.1339 B.133 C.6 1.1340 B.134 C.61.1341 B.135 C.6 1.1342 B.136 C.6 1.1343 B.137 C.6 1.1344 B.138 C.61.1345 B.139 C.6 1.1346 B.140 C.6 1.1347 B.141 C.6 1.1348 B.142 C.61.1349 B.143 C.6 1.1350 B.144 C.6 1.1351 B.145 C.6 1.1352 B.146 C.61.1353 B.147 C.6 1.1354 B.148 C.6 1.1355 B.149 C.6 1.1356 B.150 C.61.1357 B.151 C.6 1.1358 B.152 C.6 1.1359 B.153 C.6 1.1360 B.154 C.61.1361 B.155 C.6 1.1362 B.156 C.6 1.1363 B.157 C.6 1.1364 B.158 C.61.1365 B.159 C.6 1.1366 B.160 C.6 1.1367 B.161 C.6 1.1368 B.162 C.61.1369 B.163 C.6 1.1370 B.164 C.6 1.1371 B.165 C.6 1.1372 B.166 C.61.1373 B.167 C.6 1.1374 B.168 C.6 1.1375 B.169 C.6 1.1376 B.170 C.61.1377 B.171 C.6 1.1378 B.172 C.6 1.1379 B.173 C.6 1.1380 B.174 C.61.1381 B.175 C.6 1.1382 B.176 C.6 1.1383 B.177 C.6 1.1384 B.178 C.61.1385 B.179 C.6 1.1386 B.180 C.6 1.1387 B.181 C.6 1.1388 B.182 C.61.1389 B.183 C.6 1.1390 B.184 C.6 1.1391 B.185 C.6 1.1392 B.186 C.61.1393 B.187 C.6 1.1394 B.188 C.6 1.1395 B.189 C.6 1.1396 B.190 C.61.1397 B.191 C.6 1.1398 B.192 C.6 1.1399 B.193 C.6 1.1400 B.194 C.61.1401 B.195 C.6 1.1402 B.196 C.6 1.1403 B.197 C.6 1.1404 B.198 C.61.1405 B.199 C.6 1.1406 B.200 C.6 1.1407 B.201 C.6 1.1408 B.1 C.7 1.1409B.2 C.7 1.1410 B.3 C.7 1.1411 B.4 C.7 1.1412 B.5 C.7 1.1413 B.6 C.71.1414 B.7 C.7 1.1415 B.8 C.7 1.1416 B.9 C.7 1.1417 B.10 C.7 1.1418 B.11C.7 1.1419 B.12 C.7 1.1420 B.13 C.7 1.1421 B.14 C.7 1.1422 B.15 C.71.1423 B.16 C.7 1.1424 B.17 C.7 1.1425 B.18 C.7 1.1426 B.19 C.7 1.1427B.20 C.7 1.1428 B.21 C.7 1.1429 B.22 C.7 1.1430 B.23 C.7 1.1431 B.24 C.71.1432 B.25 C.7 1.1433 B.26 C.7 1.1434 B.27 C.7 1.1435 B.28 C.7 1.1436B.29 C.7 1.1437 B.30 C.7 1.1438 B.31 C.7 1.1439 B.32 C.7 1.1440 B.33 C.71.1441 B.34 C.7 1.1442 B.35 C.7 1.1443 B.36 C.7 1.1444 B.37 C.7 1.1445B.38 C.7 1.1446 B.39 C.7 1.1447 B.40 C.7 1.1448 B.41 C.7 1.1449 B.42 C.71.1450 B.43 C.7 1.1451 B.44 C.7 1.1452 B.45 C.7 1.1453 B.46 C.7 1.1454B.47 C.7 1.1455 B.48 C.7 1.1456 B.49 C.7 1.1457 B.50 C.7 1.1458 B.51 C.71.1459 B.52 C.7 1.1460 B.53 C.7 1.1461 B.54 C.7 1.1462 B.55 C.7 1.1463B.56 C.7 1.1464 B.57 C.7 1.1465 B.58. C.7 1.1466 B.59 C.7 1.1467 B.60C.7 1.1468 B.61 C.7 1.1469 B.62 C.7 1.1470 B.63 C.7 1.1471 B.64 C.71.1472 B.65 C.7 1.1473 B.66 C.7 1.1474 B.67 C.7 1.1475 B.68 C.7 1.1476B.69 C.7 1.1477 B.70 C.7 1.1478 B.71 C.7 1.1479 B.72 C.7 1.1480 B.73 C.71.1481 B.74 C.7 1.1482 B.75 C.7 1.1483 B.76 C.7 1.1484 B.77 C.7 1.1485B.78 C.7 1.1486 B.79 C.7 1.1487 B.80 C.7 1.1488 B.81 C.7 1.1489 B.82 C.71.1490 B.83 C.7 1.1491 B.84 C.7 1.1492 B.85 C.7 1.1493 B.86 C.7 1.1494B.87 C.7 1.1495 B.88 C.7 1.1496 B.89 C.7 1.1497 B.90 C.7 1.1498 B.91 C.71.1499 B.92 C.7 1.1500 B.93 C.7 1.1501 B.94 C.7 1.1502 B.95 C.7 1.1503B.96 C.7 1.1504 B.97 C.7 1.1505 B.98 C.7 1.1506 B.99 C.7 1.1507 B.100C.7 1.1508 B.101 C.7 1.1509 B.102 C.7 1.1510 B.103 C.7 1.1511 B.104 C.71.1512 B.105 C.7 1.1513 B.106 C.7 1.1514 B.107 C.7 1.1515 B.108 C.71.1516 B.109 C.7 1.1517 B.110 C.7 1.1518 B.111 C.7 1.1519 B.112 C.71.1520 B.113 C.7 1.1521 B.114 C.7 1.1522 B.115 C.7 1.1523 B.116 C.71.1524 B.117 C.7 1.1525 B.118 C.7 1.1526 B.119 C.7 1.1527 B.120 C.71.1528 B.121 C.7 1.1529 B.122 C.7 1.1530 B.123 C.7 1.1531 B.124 C.71.1532 B.125 C.7 1.1533 B.126 C.7 1.1534 B.127 C.7 1.1535 B.128 C.71.1536 B.129 C.7 1.1537 B.130 C.7 1.1538 B.131 C.7 1.1539 B.132 C.71.1540 B.133 C.7 1.1541 B.134 C.7 1.1542 B.135 C.7 1.1543 B.136 C.71.1544 B.137 C.7 1.1545 B.138 C.7 1.1546 B.139 C.7 1.1547 B.140 C.71.1548 B.141 C.7 1.1549 B.142 C.7 1.1550 B.143 C.7 1.1551 B.144 C.71.1552 B.145 C.7 1.1553 B.146 C.7 1.1554 B.147 C.7 1.1555 B.148 C.71.1556 B.149 C.7 1.1557 B.150 C.7 1.1558 B.151 C.7 1.1559 B.152 C.71.1560 B.153 C.7 1.1561 B.154 C.7 1.1562 B.155 C.7 1.1563 B.156 C.71.1564 B.157 C.7 1.1565 B.158 C.7 1.1566 B.159 C.7 1.1567 B.160 C.71.1568 B.161 C.7 1.1569 B.162 C.7 1.1570 B.163 C.7 1.1571 B.164 C.71.1572 B.165 C.7 1.1573 B.166 C.7 1.1574 B.167 C.7 1.1575 B.168 C.71.1576 B.169 C.7 1.1577 B.170 C.7 1.1578 B.171 C.7 1.1579 B.172 C.71.1580 B.173 C.7 1.1581 B.174 C.7 1.1582 B.175 C.7 1.1583 B.176 C.71.1584 B.177 C.7 1.1585 B.178 C.7 1.1586 B.179 C.7 1.1587 B.180 C.71.1588 B.181 C.7 1.1589 B.182 C.7 1.1590 B.183 C.7 1.1591 B.184 C.71.1592 B.185 C.7 1.1593 B.186 C.7 1.1594 B.187 C.7 1.1595 B.188 C.71.1596 B.189 C.7 1.1597 B.190 C.7 1.1598 B.191 C.7 1.1599 B.192 C.71.1600 B.193 C.7 1.1601 B.194 C.7 1.1602 B.195 C.7 1.1603 B.196 C.71.1604 B.197 C.7 1.1605 B.198 C.7 1.1606 B.199 C.7 1.1607 B.200 C.71.1608 B.201 C.7 1.1609 B.1 C.8 1.1610 B.2 C.8 1.1611 B.3 C.8 1.1612 B.4C.8 1.1613 B.5 C.8 1.1614 B.6 C.8 1.1615 B.7 C.8 1.1616 B.8 C.8 1.1617B.9 C.8 1.1618 B.10 C.8 1.1619 B.11 C.8 1.1620 B.12 C.8 1.1621 B.13 C.81.1622 B.14 C.8 1.1623 B.15 C.8 1.1624 B.16 C.8 1.1625 B.17 C.8 1.1626B.18 C.8 1.1627 B.19 C.8 1.1628 B.20 C.8 1.1629 B.21 C.8 1.1630 B.22 C.81.1631 B.23 C.8 1.1632 B.24 C.8 1.1633 B.25 C.8 1.1634 B.26 C.8 1.1635B.27 C.8 1.1636 B.28 C.8 1.1637 B.29 C.8 1.1638 B.30 C.8 1.1639 B.31 C.81.1640 B.32 C.8 1.1641 B.33 C.8 1.1642 B.34 C.8 1.1643 B.35 C.8 1.1644B.36 C.8 1.1645 B.37 C.8 1.1646 B.38 C.8 1.1647 B.39 C.8 1.1648 B.40 C.81.1649 B.41 C.8 1.1650 B.42 C.8 1.1651 B.43 C.8 1.1652 B.44 C.8 1.1653B.45 C.8 1.1654 B.46 C.8 1.1655 B.47 C.8 1.1656 B.48 C.8 1.1657 B.49 C.81.1658 B.50 C.8 1.1659 B.51 C.8 1.1660 B.52 C.8 1.1661 B.53 C.8 1.1662B.54 C.8 1.1663 B.55 C.8 1.1664 B.56 C.8 1.1665 B.57 C.8 1.1666 B.58.C.8 1.1667 B.59 C.8 1.1668 B.60 C.8 1.1669 B.61 C.8 1.1670 B.62 C.81.1671 B.63 C.8 1.1672 B.64 C.8 1.1673 B.65 C.8 1.1674 B.66 C.8 1.1675B.67 C.8 1.1676 B.68 C.8 1.1677 B.69 C.8 1.1678 B.70 C.8 1.1679 B.71 C.81.1680 B.72 C.8 1.1681 B.73 C.8 1.1682 B.74 C.8 1.1683 B.75 C.8 1.1684B.76 C.8 1.1685 B.77 C.8 1.1686 B.78 C.8 1.1687 B.79 C.8 1.1688 B.80 C.81.1689 B.81 C.8 1.1690 B.82 C.8 1.1691 B.83 C.8 1.1692 B.84 C.8 1.1693B.85 C.8 1.1694 B.86 C.8 1.1695 B.87 C.8 1.1696 B.88 C.8 1.1697 B.89 C.81.1698 B.90 C.8 1.1699 B.91 C.8 1.1700 B.92 C.8 1.1701 B.93 C.8 1.1702B.94 C.8 1.1703 B.95 C.8 1.1704 B.96 C.8 1.1705 B.97 C.8 1.1706 B.98 C.81.1707 B.99 C.8 1.1708 B.100 C.8 1.1709 B.101 C.8 1.1710 B.102 C.81.1711 B.103 C.8 1.1712 B.104 C.8 1.1713 B.105 C.8 1.1714 B.106 C.81.1715 B.107 C.8 1.1716 B.108 C.8 1.1717 B.109 C.8 1.1718 B.110 C.81.1719 B.111 C.8 1.1720 B.112 C.8 1.1721 B.113 C.8 1.1722 B.114 C.81.1723 B.115 C.8 1.1724 B.116 C.8 1.1725 B.117 C.8 1.1726 B.118 C.81.1727 B.119 C.8 1.1728 B.120 C.8 1.1729 B.121 C.8 1.1730 B.122 C.81.1731 B.123 C.8 1.1732 B.124 C.8 1.1733 B.125 C.8 1.1734 B.126 C.81.1735 B.127 C.8 1.1736 B.128 C.8 1.1737 B.129 C.8 1.1738 B.130 C.81.1739 B.131 C.8 1.1740 B.132 C.8 1.1741 B.133 C.8 1.1742 B.134 C.81.1743 B.135 C.8 1.1744 B.136 C.8 1.1745 B.137 C.8 1.1746 B.138 C.81.1747 B.139 C.8 1.1748 B.140 C.8 1.1749 B.141 C.8 1.1750 B.142 C.81.1751 B.143 C.8 1.1752 B.144 C.8 1.1753 B.145 C.8 1.1754 B.146 C.81.1755 B.147 C.8 1.1756 B.148 C.8 1.1757 B.149 C.8 1.1758 B.150 C.81.1759 B.151 C.8 1.1760 B.152 C.8 1.1761 B.153 C.8 1.1762 B.154 C.81.1763 B.155 C.8 1.1764 B.156 C.8 1.1765 B.157 C.8 1.1766 B.158 C.81.1767 B.159 C.8 1.1768 B.160 C.8 1.1769 B.161 C.8 1.1770 B.162 C.81.1771 B.163 C.8 1.1772 B.164 C.8 1.1773 B.165 C.8 1.1774 B.166 C.81.1775 B.167 C.8 1.1776 B.168 C.8 1.1777 B.169 C.8 1.1778 B.170 C.81.1779 B.171 C.8 1.1780 B.172 C.8 1.1781 B.173 C.8 1.1782 B.174 C.81.1783 B.175 C.8 1.1784 B.176 C.8 1.1785 B.177 C.8 1.1786 B.178 C.81.1787 B.179 C.8 1.1788 B.180 C.8 1.1789 B.181 C.8 1.1790 B.182 C.81.1791 B.183 C.8 1.1792 B.184 C.8 1.1793 B.185 C.8 1.1794 B.186 C.81.1795 B.187 C.8 1.1796 B.188 C.8 1.1797 B.189 C.8 1.1798 B.190 C.81.1799 B.191 C.8 1.1800 B.192 C.8 1.1801 B.193 C.8 1.1802 B.194 C.81.1803 B.195 C.8 1.1804 B.196 C.8 1.1805 B.197 C.8 1.1806 B.198 C.81.1807 B.199 C.8 1.1808 B.200 C.8 1.1809 B.201 C.8 1.1810 B.1 C.9 1.1811B.2 C.9 1.1812 B.3 C.9 1.1813 B.4 C.9 1.1814 B.5 C.9 1.1815 B.6 C.91.1816 B.7 C.9 1.1817 B.8 C.9 1.1818 B.9 C.9 1.1819 B.10 C.9 1.1820 B.11C.9 1.1821 B.12 C.9 1.1822 B.13 C.9 1.1823 B.14 C.9 1.1824 B.15 C.91.1825 B.16 C.9 1.1826 B.17 C.9 1.1827 B.18 C.9 1.1828 B.19 C.9 1.1829B.20 C.9 1.1830 B.21 C.9 1.1831 B.22 C.9 1.1832 B.23 C.9 1.1833 B.24 C.91.1834 B.25 C.9 1.1835 B.26 C.9 1.1836 B.27 C.9 1.1837 B.28 C.9 1.1838B.29 C.9 1.1839 B.30 C.9 1.1840 B.31 C.9 1.1841 B.32 C.9 1.1842 B.33 C.91.1843 B.34 C.9 1.1844 B.35 C.9 1.1845 B.36 C.9 1.1846 B.37 C.9 1.1847B.38 C.9 1.1848 B.39 C.9 1.1849 B.40 C.9 1.1850 B.41 C.9 1.1851 B.42 C.91.1852 B.43 C.9 1.1853 B.44 C.9 1.1854 B.45 C.9 1.1855 B.46 C.9 1.1856B.47 C.9 1.1857 B.48 C.9 1.1858 B.49 C.9 1.1859 B.50 C.9 1.1860 B.51 C.91.1861 B.52 C.9 1.1862 B.53 C.9 1.1863 B.54 C.9 1.1864 B.55 C.9 1.1865B.56 C.9 1.1866 B.57 C.9 1.1867 B.58. C.9 1.1868 B.59 C.9 1.1869 B.60C.9 1.1870 B.61 C.9 1.1871 B.62 C.9 1.1872 B.63 C.9 1.1873 B.64 C.91.1874 B.65 C.9 1.1875 B.66 C.9 1.1876 B.67 C.9 1.1877 B.68 C.9 1.1878B.69 C.9 1.1879 B.70 C.9 1.1880 B.71 C.9 1.1881 B.72 C.9 1.1882 B.73 C.91.1883 B.74 C.9 1.1884 B.75 C.9 1.1885 B.76 C.9 1.1886 B.77 C.9 1.1887B.78 C.9 1.1888 B.79 C.9 1.1889 B.80 C.9 1.1890 B.81 C.9 1.1891 B.82 C.91.1892 B.83 C.9 1.1893 B.84 C.9 1.1894 B.85 C.9 1.1895 B.86 C.9 1.1896B.87 C.9 1.1897 B.88 C.9 1.1898 B.89 C.9 1.1899 B.90 C.9 1.1900 B.91 C.91.1901 B.92 C.9 1.1902 B.93 C.9 1.1903 B.94 C.9 1.1904 B.95 C.9 1.1905B.96 C.9 1.1906 B.97 C.9 1.1907 B.98 C.9 1.1908 B.99 C.9 1.1909 B.100C.9 1.1910 B.101 C.9 1.1911 B.102 C.9 1.1912 B.103 C.9 1.1913 B.104 C.91.1914 B.105 C.9 1.1915 B.106 C.9 1.1916 B.107 C.9 1.1917 B.108 C.91.1918 B.109 C.9 1.1919 B.110 C.9 1.1920 B.111 C.9 1.1921 B.112 C.91.1922 B.113 C.9 1.1923 B.114 C.9 1.1924 B.115 C.9 1.1925 B.116 C.91.1926 B.117 C.9 1.1927 B.118 C.9 1.1928 B.119 C.9 1.1929 B.120 C.91.1930 B.121 C.9 1.1931 B.122 C.9 1.1932 B.123 C.9 1.1933 B.124 C.91.1934 B.125 C.9 1.1935 B.126 C.9 1.1936 B.127 C.9 1.1937 B.128 C.91.1938 B.129 C.9 1.1939 B.130 C.9 1.1940 B.131 C.9 1.1941 B.132 C.91.1942 B.133 C.9 1.1943 B.134 C.9 1.1944 B.135 C.9 1.1945 B.136 C.91.1946 B.137 C.9 1.1947 B.138 C.9 1.1948 B.139 C.9 1.1949 B.140 C.91.1950 B.141 C.9 1.1951 B.142 C.9 1.1952 B.143 C.9 1.1953 B.144 C.91.1954 B.145 C.9 1.1955 B.146 C.9 1.1956 B.147 C.9 1.1957 B.148 C.91.1958 B.149 C.9 1.1959 B.150 C.9 1.1960 B.151 C.9 1.1961 B.152 C.91.1962 B.153 C.9 1.1963 B.154 C.9 1.1964 B.155 C.9 1.1965 B.156 C.91.1966 B.157 C.9 1.1967 B.158 C.9 1.1968 B.159 C.9 1.1969 B.160 C.91.1970 B.161 C.9 1.1971 B.162 C.9 1.1972 B.163 C.9 1.1973 B.164 C.91.1974 B.165 C.9 1.1975 B.166 C.9 1.1976 B.167 C.9 1.1977 B.168 C.91.1978 B.169 C.9 1.1979 B.170 C.9 1.1980 B.171 C.9 1.1981 B.172 C.91.1982 B.173 C.9 1.1983 B.174 C.9 1.1984 B.175 C.9 1.1985 B.176 C.91.1986 B.177 C.9 1.1987 B.178 C.9 1.1988 B.179 C.9 1.1989 B.180 C.91.1990 B.181 C.9 1.1991 B.182 C.9 1.1992 B.183 C.9 1.1993 B.184 C.91.1994 B.185 C.9 1.1995 B.186 C.9 1.1996 B.187 C.9 1.1997 B.188 C.91.1998 B.189 C.9 1.1999 B.190 C.9 1.2000 B.191 C.9 1.2001 B.192 C.91.2002 B.193 C.9 1.2003 B.194 C.9 1.2004 B.195 C.9 1.2005 B.196 C.91.2006 B.197 C.9 1.2007 B.198 C.9 1.2008 B.199 C.9 1.2009 B.200 C.91.2010 B.201 C.9 1.2011 B.1 C.10 1.2012 B.2 C.10 1.2013 B.3 C.10 1.2014B.4 C.10 1.2015 B.5 C.10 1.2016 B.6 C.10 1.2017 B.7 C.10 1.2018 B.8 C.101.2019 B.9 C.10 1.2020 B.10 C.10 1.2021 B.11 C.10 1.2022 B.12 C.101.2023 B.13 C.10 1.2024 B.14 C.10 1.2025 B.15 C.10 1.2026 B.16 C.101.2027 B.17 C.10 1.2028 B.18 C.10 1.2029 B.19 C.10 1.2030 B.20 C.101.2031 B.21 C.10 1.2032 B.22 C.10 1.2033 B.23 C.10 1.2034 B.24 C.101.2035 B.25 C.10 1.2036 B.26 C.10 1.2037 B.27 C.10 1.2038 B.28 C.101.2039 B.29 C.10 1.2040 B.30 C.10 1.2041 B.31 C.10 1.2042 B.32 C.101.2043 B.33 C.10 1.2044 B.34 C.10 1.2045 B.35 C.10 1.2046 B.36 C.101.2047 B.37 C.10 1.2048 B.38 C.10 1.2049 B.39 C.10 1.2050 B.40 C.101.2051 B.41 C.10 1.2052 B.42 C.10 1.2053 B.43 C.10 1.2054 B.44 C.101.2055 B.45 C.10 1.2056 B.46 C.10 1.2057 B.47 C.10 1.2058 B.48 C.101.2059 B.49 C.10 1.2060 B.50 C.10 1.2061 B.51 C.10 1.2062 B.52 C.101.2063 B.53 C.10 1.2064 B.54 C.10 1.2065 B.55 C.10 1.2066 B.56 C.101.2067 B.57 C.10 1.2068 B.58. C.10 1.2069 B.59 C.10 1.2070 B.60 C.101.2071 B.61 C.10 1.2072 B.62 C.10 1.2073 B.63 C.10 1.2074 B.64 C.101.2075 B.65 C.10 1.2076 B.66 C.10 1.2077 B.67 C.10 1.2078 B.68 C.101.2079 B.69 C.10 1.2080 B.70 C.10 1.2081 B.71 C.10 1.2082 B.72 C.101.2083 B.73 C.10 1.2084 B.74 C.10 1.2085 B.75 C.10 1.2086 B.76 C.101.2087 B.77 C.10 1.2088 B.78 C.10 1.2089 B.79 C.10 1.2090 B.80 C.101.2091 B.81 C.10 1.2092 B.82 C.10 1.2093 B.83 C.10 1.2094 B.84 C.101.2095 B.85 C.10 1.2096 B.86 C.10 1.2097 B.87 C.10 1.2098 B.88 C.101.2099 B.89 C.10 1.2100 B.90 C.10 1.2101 B.91 C.10 1.2102 B.92 C.101.2103 B.93 C.10 1.2104 B.94 C.10 1.2105 B.95 C.10 1.2106 B.96 C.101.2107 B.97 C.10 1.2108 B.98 C.10 1.2109 B.99 C.10 1.2110 B.100 C.101.2111 B.101 C.10 1.2112 B.102 C.10 1.2113 B.103 C.10 1.2114 B.104 C.101.2115 B.105 C.10 1.2116 B.106 C.10 1.2117 B.107 C.10 1.2118 B.108 C.101.2119 B.109 C.10 1.2120 B.110 C.10 1.2121 B.111 C.10 1.2122 B.112 C.101.2123 B.113 C.10 1.2124 B.114 C.10 1.2125 B.115 C.10 1.2126 B.116 C.101.2127 B.117 C.10 1.2128 B.118 C.10 1.2129 B.119 C.10 1.2130 B.120 C.101.2131 B.121 C.10 1.2132 B.122 C.10 1.2133 B.123 C.10 1.2134 B.124 C.101.2135 B.125 C.10 1.2136 B.126 C.10 1.2137 B.127 C.10 1.2138 B.128 C.101.2139 B.129 C.10 1.2140 B.130 C.10 1.2141 B.131 C.10 1.2142 B.132 C.101.2143 B.133 C.10 1.2144 B.134 C.10 1.2145 B.135 C.10 1.2146 B.136 C.101.2147 B.137 C.10 1.2148 B.138 C.10 1.2149 B.139 C.10 1.2150 B.140 C.101.2151 B.141 C.10 1.2152 B.142 C.10 1.2153 B.143 C.10 1.2154 B.144 C.101.2155 B.145 C.10 1.2156 B.146 C.10 1.2157 B.147 C.10 1.2158 B.148 C.101.2159 B.149 C.10 1.2160 B.150 C.10 1.2161 B.151 C.10 1.2162 B.152 C.101.2163 B.153 C.10 1.2164 B.154 C.10 1.2165 B.155 C.10 1.2166 B.156 C.101.2167 B.157 C.10 1.2168 B.158 C.10 1.2169 B.159 C.10 1.2170 B.160 C.101.2171 B.161 C.10 1.2172 B.162 C.10 1.2173 B.163 C.10 1.2174 B.164 C.101.2175 B.165 C.10 1.2176 B.166 C.10 1.2177 B.167 C.10 1.2178 B.168 C.101.2179 B.169 C.10 1.2180 B.170 C.10 1.2181 B.171 C.10 1.2182 B.172 C.101.2183 B.173 C.10 1.2184 B.174 C.10 1.2185 B.175 C.10 1.2186 B.176 C.101.2187 B.177 C.10 1.2188 B.178 C.10 1.2189 B.179 C.10 1.2190 B.180 C.101.2191 B.181 C.10 1.2192 B.182 C.10 1.2193 B.183 C.10 1.2194 B.184 C.101.2195 B.185 C.10 1.2196 B.186 C.10 1.2197 B.187 C.10 1.2198 B.188 C.101.2199 B.189 C.10 1.2200 B.190 C.10 1.2201 B.191 C.10 1.2202 B.192 C.101.2203 B.193 C.10 1.2204 B.194 C.10 1.2205 B.195 C.10 1.2206 B.196 C.101.2207 B.197 C.10 1.2208 B.198 C.10 1.2209 B.199 C.10 1.2210 B.200 C.101.2211 B.201 C.10 1.2212 B.1 C.11 1.2213 B.2 C.11 1.2214 B.3 C.11 1.2215B.4 C.11 1.2216 B.5 C.11 1.2217 B.6 C.11 1.2218 B.7 C.11 1.2219 B.8 C.111.2220 B.9 C.11 1.2221 B.10 C.11 1.2222 B.11 C.11 1.2223 B.12 C.111.2224 B.13 C.11 1.2225 B.14 C.11 1.2226 B.15 C.11 1.2227 B.16 C.111.2228 B.17 C.11 1.2229 B.18 C.11 1.2230 B.19 C.11 1.2231 B.20 C.111.2232 B.21 C.11 1.2233 B.22 C.11 1.2234 B.23 C.11 1.2235 B.24 C.111.2236 B.25 C.11 1.2237 B.26 C.11 1.2238 B.27 C.11 1.2239 B.28 C.111.2240 B.29 C.11 1.2241 B.30 C.11 1.2242 B.31 C.11 1.2243 B.32 C.111.2244 B.33 C.11 1.2245 B.34 C.11 1.2246 B.35 C.11 1.2247 B.36 C.111.2248 B.37 C.11 1.2249 B.38 C.11 1.2250 B.39 C.11 1.2251 B.40 C.111.2252 B.41 C.11 1.2253 B.42 C.11 1.2254 B.43 C.11 1.2255 B.44 C.111.2256 B.45 C.11 1.2257 B.46 C.11 1.2258 B.47 C.11 1.2259 B.48 C.111.2260 B.49 C.11 1.2261 B.50 C.11 1.2262 B.51 C.11 1.2263 B.52 C.111.2264 B.53 C.11 1.2265 B.54 C.11 1.2266 B.55 C.11 1.2267 B.56 C.111.2268 B.57 C.11 1.2269 B.58. C.11 1.2270 B.59 C.11 1.2271 B.60 C.111.2272 B.61 C.11 1.2273 B.62 C.11 1.2274 B.63 C.11 1.2275 B.64 C.111.2276 B.65 C.11 1.2277 B.66 C.11 1.2278 B.67 C.11 1.2279 B.68 C.111.2280 B.69 C.11 1.2281 B.70 C.11 1.2282 B.71 C.11 1.2283 B.72 C.111.2284 B.73 C.11 1.2285 B.74 C.11 1.2286 B.75 C.11 1.2287 B.76 C.111.2288 B.77 C.11 1.2289 B.78 C.11 1.2290 B.79 C.11 1.2291 B.80 C.111.2292 B.81 C.11 1.2293 B.82 C.11 1.2294 B.83 C.11 1.2295 B.84 C.111.2296 B.85 C.11 1.2297 B.86 C.11 1.2298 B.87 C.11 1.2299 B.88 C.111.2300 B.89 C.11 1.2301 B.90 C.11 1.2302 B.91 C.11 1.2303 B.92 C.111.2304 B.93 C.11 1.2305 B.94 C.11 1.2306 B.95 C.11 1.2307 B.96 C.111.2308 B.97 C.11 1.2309 B.98 C.11 1.2310 B.99 C.11 1.2311 B.100 C.111.2312 B.101 C.11 1.2313 B.102 C.11 1.2314 B.103 C.11 1.2315 B.104 C.111.2316 B.105 C.11 1.2317 B.106 C.11 1.2318 B.107 C.11 1.2319 B.108 C.111.2320 B.109 C.11 1.2321 B.110 C.11 1.2322 B.111 C.11 1.2323 B.112 C.111.2324 B.113 C.11 1.2325 B.114 C.11 1.2326 B.115 C.11 1.2327 B.116 C.111.2328 B.117 C.11 1.2329 B.118 C.11 1.2330 B.119 C.11 1.2331 B.120 C.111.2332 B.121 C.11 1.2333 B.122 C.11 1.2334 B.123 C.11 1.2335 B.124 C.111.2336 B.125 C.11 1.2337 B.126 C.11 1.2338 B.127 C.11 1.2339 B.128 C.111.2340 B.129 C.11 1.2341 B.130 C.11 1.2342 B.131 C.11 1.2343 B.132 C.111.2344 B.133 C.11 1.2345 B.134 C.11 1.2346 B.135 C.11 1.2347 B.136 C.111.2348 B.137 C.11 1.2349 B.138 C.11 1.2350 B.139 C.11 1.2351 B.140 C.111.2352 B.141 C.11 1.2353 B.142 C.11 1.2354 B.143 C.11 1.2355 B.144 C.111.2356 B.145 C.11 1.2357 B.146 C.11 1.2358 B.147 C.11 1.2359 B.148 C.111.2360 B.149 C.11 1.2361 B.150 C.11 1.2362 B.151 C.11 1.2363 B.152 C.111.2364 B.153 C.11 1.2365 B.154 C.11 1.2366 B.155 C.11 1.2367 B.156 C.111.2368 B.157 C.11 1.2369 B.158 C.11 1.2370 B.159 C.11 1.2371 B.160 C.111.2372 B.161 C.11 1.2373 B.162 C.11 1.2374 B.163 C.11 1.2375 B.164 C.111.2376 B.165 C.11 1.2377 B.166 C.11 1.2378 B.167 C.11 1.2379 B.168 C.111.2380 B.169 C.11 1.2381 B.170 C.11 1.2382 B.171 C.11 1.2383 B.172 C.111.2384 B.173 C.11 1.2385 B.174 C.11 1.2386 B.175 C.11 1.2387 B.176 C.111.2388 B.177 C.11 1.2389 B.178 C.11 1.2390 B.179 C.11 1.2391 B.180 C.111.2392 B.181 C.11 1.2393 B.182 C.11 1.2394 B.183 C.11 1.2395 B.184 C.111.2396 B.185 C.11 1.2397 B.186 C.11 1.2398 B.187 C.11 1.2399 B.188 C.111.2400 B.189 C.11 1.2401 B.190 C.11 1.2402 B.191 C.11 1.2403 B.192 C.111.2404 B.193 C.11 1.2405 B.194 C.11 1.2406 B.195 C.11 1.2407 B.196 C.111.2408 B.197 C.11 1.2409 B.198 C.11 1.2410 B.199 C.11 1.2411 B.200 C.111.2412 B.201 C.11 1.2413 B.1 C.12 1.2414 B.2 C.12 1.2415 B.3 C.12 1.2416B.4 C.12 1.2417 B.5 C.12 1.2418 B.6 C.12 1.2419 B.7 C.12 1.2420 B.8 C.121.2421 B.9 C.12 1.2422 B.10 C.12 1.2423 B.11 C.12 1.2424 B.12 C.121.2425 B.13 C.12 1.2426 B.14 C.12 1.2427 B.15 C.12 1.2428 B.16 C.121.2429 B.17 C.12 1.2430 B.18 C.12 1.2431 B.19 C.12 1.2432 B.20 C.121.2433 B.21 C.12 1.2434 B.22 C.12 1.2435 B.23 C.12 1.2436 B.24 C.121.2437 B.25 C.12 1.2438 B.26 C.12 1.2439 B.27 C.12 1.2440 B.28 C.121.2441 B.29 C.12 1.2442 B.30 C.12 1.2443 B.31 C.12 1.2444 B.32 C.121.2445 B.33 C.12 1.2446 B.34 C.12 1.2447 B.35 C.12 1.2448 B.36 C.121.2449 B.37 C.12 1.2450 B.38 C.12 1.2451 B.39 C.12 1.2452 B.40 C.121.2453 B.41 C.12 1.2454 B.42 C.12 1.2455 B.43 C.12 1.2456 B.44 C.121.2457 B.45 C.12 1.2458 B.46 C.12 1.2459 B.47 C.12 1.2460 B.48 C.121.2461 B.49 C.12 1.2462 B.50 C.12 1.2463 B.51 C.12 1.2464 B.52 C.121.2465 B.53 C.12 1.2466 B.54 C.12 1.2467 B.55 C.12 1.2468 B.56 C.121.2469 B.57 C.12 1.2470 B.58. C.12 1.2471 B.59 C.12 1.2472 B.60 C.121.2473 B.61 C.12 1.2474 B.62 C.12 1.2475 B.63 C.12 1.2476 B.64 C.121.2477 B.65 C.12 1.2478 B.66 C.12 1.2479 B.67 C.12 1.2480 B.68 C.121.2481 B.69 C.12 1.2482 B.70 C.12 1.2483 B.71 C.12 1.2484 B.72 C.121.2485 B.73 C.12 1.2486 B.74 C.12 1.2487 B.75 C.12 1.2488 B.76 C.121.2489 B.77 C.12 1.2490 B.78 C.12 1.2491 B.79 C.12 1.2492 B.80 C.121.2493 B.81 C.12 1.2494 B.82 C.12 1.2495 B.83 C.12 1.2496 B.84 C.121.2497 B.85 C.12 1.2498 B.86 C.12 1.2499 B.87 C.12 1.2500 B.88 C.121.2501 B.89 C.12 1.2502 B.90 C.12 1.2503 B.91 C.12 1.2504 B.92 C.121.2505 B.93 C.12 1.2506 B.94 C.12 1.2507 B.95 C.12 1.2508 B.96 C.121.2509 B.97 C.12 1.2510 B.98 C.12 1.2511 B.99 C.12 1.2512 B.100 C.121.2513 B.101 C.12 1.2514 B.102 C.12 1.2515 B.103 C.12 1.2516 B.104 C.121.2517 B.105 C.12 1.2518 B.106 C.12 1.2519 B.107 C.12 1.2520 B.108 C.121.2521 B.109 C.12 1.2522 B.110 C.12 1.2523 B.111 C.12 1.2524 B.112 C.121.2525 B.113 C.12 1.2526 B.114 C.12 1.2527 B.115 C.12 1.2528 B.116 C.121.2529 B.117 C.12 1.2530 B.118 C.12 1.2531 B.119 C.12 1.2532 B.120 C.121.2533 B.121 C.12 1.2534 B.122 C.12 1.2535 B.123 C.12 1.2536 B.124 C.121.2537 B.125 C.12 1.2538 B.126 C.12 1.2539 B.127 C.12 1.2540 B.128 C.121.2541 B.129 C.12 1.2542 B.130 C.12 1.2543 B.131 C.12 1.2544 B.132 C.121.2545 B.133 C.12 1.2546 B.134 C.12 1.2547 B.135 C.12 1.2548 B.136 C.121.2549 B.137 C.12 1.2550 B.138 C.12 1.2551 B.139 C.12 1.2552 B.140 C.121.2553 B.141 C.12 1.2554 B.142 C.12 1.2555 B.143 C.12 1.2556 B.144 C.121.2557 B.145 C.12 1.2558 B.146 C.12 1.2559 B.147 C.12 1.2560 B.148 C.121.2561 B.149 C.12 1.2562 B.150 C.12 1.2563 B.151 C.12 1.2564 B.152 C.121.2565 B.153 C.12 1.2566 B.154 C.12 1.2567 B.155 C.12 1.2568 B.156 C.121.2569 B.157 C.12 1.2570 B.158 C.12 1.2571 B.159 C.12 1.2572 B.160 C.121.2573 B.161 C.12 1.2574 B.162 C.12 1.2575 B.163 C.12 1.2576 B.164 C.121.2577 B.165 C.12 1.2578 B.166 C.12 1.2579 B.167 C.12 1.2580 B.168 C.121.2581 B.169 C.12 1.2582 B.170 C.12 1.2583 B.171 C.12 1.2584 B.172 C.121.2585 B.173 C.12 1.2586 B.174 C.12 1.2587 B.175 C.12 1.2588 B.176 C.121.2589 B.177 C.12 1.2590 B.178 C.12 1.2591 B.179 C.12 1.2592 B.180 C.121.2593 B.181 C.12 1.2594 B.182 C.12 1.2595 B.183 C.12 1.2596 B.184 C.121.2597 B.185 C.12 1.2598 B.186 C.12 1.2599 B.187 C.12 1.2600 B.188 C.121.2601 B.189 C.12 1.2602 B.190 C.12 1.2603 B.191 C.12 1.2604 B.192 C.121.2605 B.193 C.12 1.2606 B.194 C.12 1.2607 B.195 C.12 1.2608 B.196 C.121.2609 B.197 C.12 1.2610 B.198 C.12 1.2611 B.199 C.12 1.2612 B.200 C.121.2613 B.201 C.12 1.2614 B.1 C.13 1.2615 B.2 C.13 1.2616 B.3 C.13 1.2617B.4 C.13 1.2618 B.5 C.13 1.2619 B.6 C.13 1.2620 B.7 C.13 1.2621 B.8 C.131.2622 B.9 C.13 1.2623 B.10 C.13 1.2624 B.11 C.13 1.2625 B.12 C.131.2626 B.13 C.13 1.2627 B.14 C.13 1.2628 B.15 C.13 1.2629 B.16 C.131.2630 B.17 C.13 1.2631 B.18 C.13 1.2632 B.19 C.13 1.2633 B.20 C.131.2634 B.21 C.13 1.2635 B.22 C.13 1.2636 B.23 C.13 1.2637 B.24 C.131.2638 B.25 C.13 1.2639 B.26 C.13 1.2640 B.27 C.13 1.2641 B.28 C.131.2642 B.29 C.13 1.2643 B.30 C.13 1.2644 B.31 C.13 1.2645 B.32 C.131.2646 B.33 C.13 1.2647 B.34 C.13 1.2648 B.35 C.13 1.2649 B.36 C.131.2650 B.37 C.13 1.2651 B.38 C.13 1.2652 B.39 C.13 1.2653 B.40 C.131.2654 B.41 C.13 1.2655 B.42 C.13 1.2656 B.43 C.13 1.2657 B.44 C.131.2658 B.45 C.13 1.2659 B.46 C.13 1.2660 B.47 C.13 1.2661 B.48 C.131.2662 B.49 C.13 1.2663 B.50 C.13 1.2664 B.51 C.13 1.2665 B.52 C.131.2666 B.53 C.13 1.2667 B.54 C.13 1.2668 B.55 C.13 1.2669 B.56 C.131.2670 B.57 C.13 1.2671 B.58. C.13 1.2672 B.59 C.13 1.2673 B.60 C.131.2674 B.61 C.13 1.2675 B.62 C.13 1.2676 B.63 C.13 1.2677 B.64 C.131.2678 B.65 C.13 1.2679 B.66 C.13 1.2680 B.67 C.13 1.2681 B.68 C.131.2682 B.69 C.13 1.2683 B.70 C.13 1.2684 B.71 C.13 1.2685 B.72 C.131.2686 B.73 C.13 1.2687 B.74 C.13 1.2688 B.75 C.13 1.2689 B.76 C.131.2690 B.77 C.13 1.2691 B.78 C.13 1.2692 B.79 C.13 1.2693 B.80 C.131.2694 B.81 C.13 1.2695 B.82 C.13 1.2696 B.83 C.13 1.2697 B.84 C.131.2698 B.85 C.13 1.2699 B.86 C.13 1.2700 B.87 C.13 1.2701 B.88 C.131.2702 B.89 C.13 1.2703 B.90 C.13 1.2704 B.91 C.13 1.2705 B.92 C.131.2706 B.93 C.13 1.2707 B.94 C.13 1.2708 B.95 C.13 1.2709 B.96 C.131.2710 B.97 C.13 1.2711 B.98 C.13 1.2712 B.99 C.13 1.2713 B.100 C.131.2714 B.101 C.13 1.2715 B.102 C.13 1.2716 B.103 C.13 1.2717 B.104 C.131.2718 B.105 C.13 1.2719 B.106 C.13 1.2720 B.107 C.13 1.2721 B.108 C.131.2722 B.109 C.13 1.2723 B.110 C.13 1.2724 B.111 C.13 1.2725 B.112 C.131.2726 B.113 C.13 1.2727 B.114 C.13 1.2728 B.115 C.13 1.2729 B.116 C.131.2730 B.117 C.13 1.2731 B.118 C.13 1.2732 B.119 C.13 1.2733 B.120 C.131.2734 B.121 C.13 1.2735 B.122 C.13 1.2736 B.123 C.13 1.2737 B.124 C.131.2738 B.125 C.13 1.2739 B.126 C.13 1.2740 B.127 C.13 1.2741 B.128 C.131.2742 B.129 C.13 1.2743 B.130 C.13 1.2744 B.131 C.13 1.2745 B.132 C.131.2746 B.133 C.13 1.2747 B.134 C.13 1.2748 B.135 C.13 1.2749 B.136 C.131.2750 B.137 C.13 1.2751 B.138 C.13 1.2752 B.139 C.13 1.2753 B.140 C.131.2754 B.141 C.13 1.2755 B.142 C.13 1.2756 B.143 C.13 1.2757 B.144 C.131.2758 B.145 C.13 1.2759 B.146 C.13 1.2760 B.147 C.13 1.2761 B.148 C.131.2762 B.149 C.13 1.2763 B.150 C.13 1.2764 B.151 C.13 1.2765 B.152 C.131.2766 B.153 C.13 1.2767 B.154 C.13 1.2768 B.155 C.13 1.2769 B.156 C.131.2770 B.157 C.13 1.2771 B.158 C.13 1.2772 B.159 C.13 1.2773 B.160 C.131.2774 B.161 C.13 1.2775 B.162 C.13 1.2776 B.163 C.13 1.2777 B.164 C.131.2778 B.165 C.13 1.2779 B.166 C.13 1.2780 B.167 C.13 1.2781 B.168 C.131.2782 B.169 C.13 1.2783 B.170 C.13 1.2784 B.171 C.13 1.2785 B.172 C.131.2786 B.173 C.13 1.2787 B.174 C.13 1.2788 B.175 C.13 1.2789 B.176 C.131.2790 B.177 C.13 1.2791 B.178 C.13 1.2792 B.179 C.13 1.2793 B.180 C.131.2794 B.181 C.13 1.2795 B.182 C.13 1.2796 B.183 C.13 1.2797 B.184 C.131.2798 B.185 C.13 1.2799 B.186 C.13 1.2800 B.187 C.13 1.2801 B.188 C.131.2802 B.189 C.13 1.2803 B.190 C.13 1.2804 B.191 C.13 1.2805 B.192 C.131.2806 B.193 C.13 1.2807 B.194 C.13 1.2808 B.195 C.13 1.2809 B.196 C.131.2810 B.197 C.13 1.2811 B.198 C.13 1.2812 B.199 C.13 1.2813 B.200 C.131.2814 B.201 C.13 1.2815 B.1 C.14 1.2816 B.2 C.14 1.2817 B.3 C.14 1.2818B.4 C.14 1.2819 B.5 C.14 1.2820 B.6 C.14 1.2821 B.7 C.14 1.2822 B.8 C.141.2823 B.9 C.14 1.2824 B.10 C.14 1.2825 B.11 C.14 1.2826 B.12 C.141.2827 B.13 C.14 1.2828 B.14 C.14 1.2829 B.15 C.14 1.2830 B.16 C.141.2831 B.17 C.14 1.2832 B.18 C.14 1.2833 B.19 C.14 1.2834 B.20 C.141.2835 B.21 C.14 1.2836 B.22 C.14 1.2837 B.23 C.14 1.2838 B.24 C.141.2839 B.25 C.14 1.2840 B.26 C.14 1.2841 B.27 C.14 1.2842 B.28 C.141.2843 B.29 C.14 1.2844 B.30 C.14 1.2845 B.31 C.14 1.2846 B.32 C.141.2847 B.33 C.14 1.2848 B.34 C.14 1.2849 B.35 C.14 1.2850 B.36 C.141.2851 B.37 C.14 1.2852 B.38 C.14 1.2853 B.39 C.14 1.2854 B.40 C.141.2855 B.41 C.14 1.2856 B.42 C.14 1.2857 B.43 C.14 1.2858 B.44 C.141.2859 B.45 C.14 1.2860 B.46 C.14 1.2861 B.47 C.14 1.2862 B.48 C.141.2863 B.49 C.14 1.2864 B.50 C.14 1.2865 B.51 C.14 1.2866 B.52 C.141.2867 B.53 C.14 1.2868 B.54 C.14 1.2869 B.55 C.14 1.2870 B.56 C.141.2871 B.57 C.14 1.2872 B.58. C.14 1.2873 B.59 C.14 1.2874 B.60 C.141.2875 B.61 C.14 1.2876 B.62 C.14 1.2877 B.63 C.14 1.2878 B.64 C.141.2879 B.65 C.14 1.2880 B.66 C.14 1.2881 B.67 C.14 1.2882 B.68 C.141.2883 B.69 C.14 1.2884 B.70 C.14 1.2885 B.71 C.14 1.2886 B.72 C.141.2887 B.73 C.14 1.2888 B.74 C.14 1.2889 B.75 C.14 1.2890 B.76 C.141.2891 B.77 C.14 1.2892 B.78 C.14 1.2893 B.79 C.14 1.2894 B.80 C.141.2895 B.81 C.14 1.2896 B.82 C.14 1.2897 B.83 C.14 1.2898 B.84 C.141.2899 B.85 C.14 1.2900 B.86 C.14 1.2901 B.87 C.14 1.2902 B.88 C.141.2903 B.89 C.14 1.2904 B.90 C.14 1.2905 B.91 C.14 1.2906 B.92 C.141.2907 B.93 C.14 1.2908 B.94 C.14 1.2909 B.95 C.14 1.2910 B.96 C.141.2911 B.97 C.14 1.2912 B.98 C.14 1.2913 B.99 C.14 1.2914 B.100 C.141.2915 B.101 C.14 1.2916 B.102 C.14 1.2917 B.103 C.14 1.2918 B.104 C.141.2919 B.105 C.14 1.2920 B.106 C.14 1.2921 B.107 C.14 1.2922 B.108 C.141.2923 B.109 C.14 1.2924 B.110 C.14 1.2925 B.111 C.14 1.2926 B.112 C.141.2927 B.113 C.14 1.2928 B.114 C.14 1.2929 B.115 C.14 1.2930 B.116 C.141.2931 B.117 C.14 1.2932 B.118 C.14 1.2933 B.119 C.14 1.2934 B.120 C.141.2935 B.121 C.14 1.2936 B.122 C.14 1.2937 B.123 C.14 1.2938 B.124 C.141.2939 B.125 C.14 1.2940 B.126 C.14 1.2941 B.127 C.14 1.2942 B.128 C.141.2943 B.129 C.14 1.2944 B.130 C.14 1.2945 B.131 C.14 1.2946 B.132 C.141.2947 B.133 C.14 1.2948 B.134 C.14 1.2949 B.135 C.14 1.2950 B.136 C.141.2951 B.137 C.14 1.2952 B.138 C.14 1.2953 B.139 C.14 1.2954 B.140 C.141.2955 B.141 C.14 1.2956 B.142 C.14 1.2957 B.143 C.14 1.2958 B.144 C.141.2959 B.145 C.14 1.2960 B.146 C.14 1.2961 B.147 C.14 1.2962 B.148 C.141.2963 B.149 C.14 1.2964 B.150 C.14 1.2965 B.151 C.14 1.2966 B.152 C.141.2967 B.153 C.14 1.2968 B.154 C.14 1.2969 B.155 C.14 1.2970 B.156 C.141.2971 B.157 C.14 1.2972 B.158 C.14 1.2973 B.159 C.14 1.2974 B.160 C.141.2975 B.161 C.14 1.2976 B.162 C.14 1.2977 B.163 C.14 1.2978 B.164 C.141.2979 B.165 C.14 1.2980 B.166 C.14 1.2981 B.167 C.14 1.2982 B.168 C.141.2983 B.169 C.14 1.2984 B.170 C.14 1.2985 B.171 C.14 1.2986 B.172 C.141.2987 B.173 C.14 1.2988 B.174 C.14 1.2989 B.175 C.14 1.2990 B.176 C.141.2991 B.177 C.14 1.2992 B.178 C.14 1.2993 B.179 C.14 1.2994 B.180 C.141.2995 B.181 C.14 1.2996 B.182 C.14 1.2997 B.183 C.14 1.2998 B.184 C.141.2999 B.185 C.14 1.3000 B.186 C.14 1.3001 B.187 C.14 1.3002 B.188 C.141.3003 B.189 C.14 1.3004 B.190 C.14 1.3005 B.191 C.14 1.3006 B.192 C.141.3007 B.193 C.14 1.3008 B.194 C.14 1.3009 B.195 C.14 1.3010 B.196 C.141.3011 B.197 C.14 1.3012 B.198 C.14 1.3013 B.199 C.14 1.3014 B.200 C.141.3015 B.201 C.14 1.3016 B.1 C.15 1.3017 B.2 C.15 1.3018 B.3 C.15 1.3019B.4 C.15 1.3020 B.5 C.15 1.3021 B.6 C.15 1.3022 B.7 C.15 1.3023 B.8 C.151.3024 B.9 C.15 1.3025 B.10 C.15 1.3026 B.11 C.15 1.3027 B.12 C.151.3028 B.13 C.15 1.3029 B.14 C.15 1.3030 B.15 C.15 1.3031 B.16 C.151.3032 B.17 C.15 1.3033 B.18 C.15 1.3034 B.19 C.15 1.3035 B.20 C.151.3036 B.21 C.15 1.3037 B.22 C.15 1.3038 B.23 C.15 1.3039 B.24 C.151.3040 B.25 C.15 1.3041 B.26 C.15 1.3042 B.27 C.15 1.3043 B.28 C.151.3044 B.29 C.15 1.3045 B.30 C.15 1.3046 B.31 C.15 1.3047 B.32 C.151.3048 B.33 C.15 1.3049 B.34 C.15 1.3050 B.35 C.15 1.3051 B.36 C.151.3052 B.37 C.15 1.3053 B.38 C.15 1.3054 B.39 C.15 1.3055 B.40 C.151.3056 B.41 C.15 1.3057 B.42 C.15 1.3058 B.43 C.15 1.3059 B.44 C.151.3060 B.45 C.15 1.3061 B.46 C.15 1.3062 B.47 C.15 1.3063 B.48 C.151.3064 B.49 C.15 1.3065 B.50 C.15 1.3066 B.51 C.15 1.3067 B.52 C.151.3068 B.53 C.15 1.3069 B.54 C.15 1.3070 B.55 C.15 1.3071 B.56 C.151.3072 B.57 C.15 1.3073 B.58. C.15 1.3074 B.59 C.15 1.3075 B.60 C.151.3076 B.61 C.15 1.3077 B.62 C.15 1.3078 B.63 C.15 1.3079 B.64 C.151.3080 B.65 C.15 1.3081 B.66 C.15 1.3082 B.67 C.15 1.3083 B.68 C.151.3084 B.69 C.15 1.3085 B.70 C.15 1.3086 B.71 C.15 1.3087 B.72 C.151.3088 B.73 C.15 1.3089 B.74 C.15 1.3090 B.75 C.15 1.3091 B.76 C.151.3092 B.77 C.15 1.3093 B.78 C.15 1.3094 B.79 C.15 1.3095 B.80 C.151.3096 B.81 C.15 1.3097 B.82 C.15 1.3098 B.83 C.15 1.3099 B.84 C.151.3100 B.85 C.15 1.3101 B.86 C.15 1.3102 B.87 C.15 1.3103 B.88 C.151.3104 B.89 C.15 1.3105 B.90 C.15 1.3106 B.91 C.15 1.3107 B.92 C.151.3108 B.93 C.15 1.3109 B.94 C.15 1.3110 B.95 C.15 1.3111 B.96 C.151.3112 B.97 C.15 1.3113 B.98 C.15 1.3114 B.99 C.15 1.3115 B.100 C.151.3116 B.101 C.15 1.3117 B.102 C.15 1.3118 B.103 C.15 1.3119 B.104 C.151.3120 B.105 C.15 1.3121 B.106 C.15 1.3122 B.107 C.15 1.3123 B.108 C.151.3124 B.109 C.15 1.3125 B.110 C.15 1.3126 B.111 C.15 1.3127 B.112 C.151.3128 B.113 C.15 1.3129 B.114 C.15 1.3130 B.115 C.15 1.3131 B.116 C.151.3132 B.117 C.15 1.3133 B.118 C.15 1.3134 B.119 C.15 1.3135 B.120 C.151.3136 B.121 C.15 1.3137 B.122 C.15 1.3138 B.123 C.15 1.3139 B.124 C.151.3140 B.125 C.15 1.3141 B.126 C.15 1.3142 B.127 C.15 1.3143 B.128 C.151.3144 B.129 C.15 1.3145 B.130 C.15 1.3146 B.131 C.15 1.3147 B.132 C.151.3148 B.133 C.15 1.3149 B.134 C.15 1.3150 B.135 C.15 1.3151 B.136 C.151.3152 B.137 C.15 1.3153 B.138 C.15 1.3154 B.139 C.15 1.3155 B.140 C.151.3156 B.141 C.15 1.3157 B.142 C.15 1.3158 B.143 C.15 1.3159 B.144 C.151.3160 B.145 C.15 1.3161 B.146 C.15 1.3162 B.147 C.15 1.3163 B.148 C.151.3164 B.149 C.15 1.3165 B.150 C.15 1.3166 B.151 C.15 1.3167 B.152 C.151.3168 B.153 C.15 1.3169 B.154 C.15 1.3170 B.155 C.15 1.3171 B.156 C.151.3172 B.157 C.15 1.3173 B.158 C.15 1.3174 B.159 C.15 1.3175 B.160 C.151.3176 B.161 C.15 1.3177 B.162 C.15 1.3178 B.163 C.15 1.3179 B.164 C.151.3180 B.165 C.15 1.3181 B.166 C.15 1.3182 B.167 C.15 1.3183 B.168 C.151.3184 B.169 C.15 1.3185 B.170 C.15 1.3186 B.171 C.15 1.3187 B.172 C.151.3188 B.173 C.15 1.3189 B.174 C.15 1.3190 B.175 C.15 1.3191 B.176 C.151.3192 B.177 C.15 1.3193 B.178 C.15 1.3194 B.179 C.15 1.3195 B.180 C.151.3196 B.181 C.15 1.3197 B.182 C.15 1.3198 B.183 C.15 1.3199 B.184 C.151.3200 B.185 C.15 1.3201 B.186 C.15 1.3202 B.187 C.15 1.3203 B.188 C.151.3204 B.189 C.15 1.3205 B.190 C.15 1.3206 B.191 C.15 1.3207 B.192 C.151.3208 B.193 C.15 1.3209 B.194 C.15 1.3210 B.195 C.15 1.3211 B.196 C.151.3212 B.197 C.15 1.3213 B.198 C.15 1.3214 B.199 C.15 1.3215 B.200 C.151.3216 B.201 C.15 1.3217 B.1 C.16 1.3218 B.2 C.16 1.3219 B.3 C.16 1.3220B.4 C.16 1.3221 B.5 C.16 1.3222 B.6 C.16 1.3223 B.7 C.16 1.3224 B.8 C.161.3225 B.9 C.16 1.3226 B.10 C.16 1.3227 B.11 C.16 1.3228 B.12 C.161.3229 B.13 C.16 1.3230 B.14 C.16 1.3231 B.15 C.16 1.3232 B.16 C.161.3233 B.17 C.16 1.3234 B.18 C.16 1.3235 B.19 C.16 1.3236 B.20 C.161.3237 B.21 C.16 1.3238 B.22 C.16 1.3239 B.23 C.16 1.3240 B.24 C.161.3241 B.25 C.16 1.3242 B.26 C.16 1.3243 B.27 C.16 1.3244 B.28 C.161.3245 B.29 C.16 1.3246 B.30 C.16 1.3247 B.31 C.16 1.3248 B.32 C.161.3249 B.33 C.16 1.3250 B.34 C.16 1.3251 B.35 C.16 1.3252 B.36 C.161.3253 B.37 C.16 1.3254 B.38 C.16 1.3255 B.39 C.16 1.3256 B.40 C.161.3257 B.41 C.16 1.3258 B.42 C.16 1.3259 B.43 C.16 1.3260 B.44 C.161.3261 B.45 C.16 1.3262 B.46 C.16 1.3263 B.47 C.16 1.3264 B.48 C.161.3265 B.49 C.16 1.3266 B.50 C.16 1.3267 B.51 C.16 1.3268 B.52 C.161.3269 B.53 C.16 1.3270 B.54 C.16 1.3271 B.55 C.16 1.3272 B.56 C.161.3273 B.57 C.16 1.3274 B.58. C.16 1.3275 B.59 C.16 1.3276 B.60 C.161.3277 B.61 C.16 1.3278 B.62 C.16 1.3279 B.63 C.16 1.3280 B.64 C.161.3281 B.65 C.16 1.3282 B.66 C.16 1.3283 B.67 C.16 1.3284 B.68 C.161.3285 B.69 C.16 1.3286 B.70 C.16 1.3287 B.71 C.16 1.3288 B.72 C.161.3289 B.73 C.16 1.3290 B.74 C.16 1.3291 B.75 C.16 1.3292 B.76 C.161.3293 B.77 C.16 1.3294 B.78 C.16 1.3295 B.79 C.16 1.3296 B.80 C.161.3297 B.81 C.16 1.3298 B.82 C.16 1.3299 B.83 C.16 1.3300 B.84 C.161.3301 B.85 C.16 1.3302 B.86 C.16 1.3303 B.87 C.16 1.3304 B.88 C.161.3305 B.89 C.16 1.3306 B.90 C.16 1.3307 B.91 C.16 1.3308 B.92 C.161.3309 B.93 C.16 1.3310 B.94 C.16 1.3311 B.95 C.16 1.3312 B.96 C.161.3313 B.97 C.16 1.3314 B.98 C.16 1.3315 B.99 C.16 1.3316 B.100 C.161.3317 B.101 C.16 1.3318 B.102 C.16 1.3319 B.103 C.16 1.3320 B.104 C.161.3321 B.105 C.16 1.3322 B.106 C.16 1.3323 B.107 C.16 1.3324 B.108 C.161.3325 B.109 C.16 1.3326 B.110 C.16 1.3327 B.111 C.16 1.3328 B.112 C.161.3329 B.113 C.16 1.3330 B.114 C.16 1.3331 B.115 C.16 1.3332 B.116 C.161.3333 B.117 C.16 1.3334 B.118 C.16 1.3335 B.119 C.16 1.3336 B.120 C.161.3337 B.121 C.16 1.3338 B.122 C.16 1.3339 B.123 C.16 1.3340 B.124 C.161.3341 B.125 C.16 1.3342 B.126 C.16 1.3343 B.127 C.16 1.3344 B.128 C.161.3345 B.129 C.16 1.3346 B.130 C.16 1.3347 B.131 C.16 1.3348 B.132 C.161.3349 B.133 C.16 1.3350 B.134 C.16 1.3351 B.135 C.16 1.3352 B.136 C.161.3353 B.137 C.16 1.3354 B.138 C.16 1.3355 B.139 C.16 1.3356 B.140 C.161.3357 B.141 C.16 1.3358 B.142 C.16 1.3359 B.143 C.16 1.3360 B.144 C.161.3361 B.145 C.16 1.3362 B.146 C.16 1.3363 B.147 C.16 1.3364 B.148 C.161.3365 B.149 C.16 1.3366 B.150 C.16 1.3367 B.151 C.16 1.3368 B.152 C.161.3369 B.153 C.16 1.3370 B.154 C.16 1.3371 B.155 C.16 1.3372 B.156 C.161.3373 B.157 C.16 1.3374 B.158 C.16 1.3375 B.159 C.16 1.3376 B.160 C.161.3377 B.161 C.16 1.3378 B.162 C.16 1.3379 B.163 C.16 1.3380 B.164 C.161.3381 B.165 C.16 1.3382 B.166 C.16 1.3383 B.167 C.16 1.3384 B.168 C.161.3385 B.169 C.16 1.3386 B.170 C.16 1.3387 B.171 C.16 1.3388 B.172 C.161.3389 B.173 C.16 1.3390 B.174 C.16 1.3391 B.175 C.16 1.3392 B.176 C.161.3393 B.177 C.16 1.3394 B.178 C.16 1.3395 B.179 C.16 1.3396 B.180 C.161.3397 B.181 C.16 1.3398 B.182 C.16 1.3399 B.183 C.16 1.3400 B.184 C.161.3401 B.185 C.16 1.3402 B.186 C.16 1.3403 B.187 C.16 1.3404 B.188 C.161.3405 B.189 C.16 1.3406 B.190 C.16 1.3407 B.191 C.16 1.3408 B.192 C.161.3409 B.193 C.16 1.3410 B.194 C.16 1.3411 B.195 C.16 1.3412 B.196 C.161.3413 B.197 C.16 1.3414 B.198 C.16 1.3415 B.199 C.16 1.3416 B.200 C.161.3417 B.201 C.16 1.3418 B.1 C.17 1.3419 B.2 C.17 1.3420 B.3 C.17 1.3421B.4 C.17 1.3422 B.5 C.17 1.3423 B.6 C.17 1.3424 B.7 C.17 1.3425 B.8 C.171.3426 B.9 C.17 1.3427 B.10 C.17 1.3428 B.11 C.17 1.3429 B.12 C.171.3430 B.13 C.17 1.3431 B.14 C.17 1.3432 B.15 C.17 1.3433 B.16 C.171.3434 B.17 C.17 1.3435 B.18 C.17 1.3436 B.19 C.17 1.3437 B.20 C.171.3438 B.21 C.17 1.3439 B.22 C.17 1.3440 B.23 C.17 1.3441 B.24 C.171.3442 B.25 C.17 1.3443 B.26 C.17 1.3444 B.27 C.17 1.3445 B.28 C.171.3446 B.29 C.17 1.3447 B.30 C.17 1.3448 B.31 C.17 1.3449 B.32 C.171.3450 B.33 C.17 1.3451 B.34 C.17 1.3452 B.35 C.17 1.3453 B.36 C.171.3454 B.37 C.17 1.3455 B.38 C.17 1.3456 B.39 C.17 1.3457 B.40 C.171.3458 B.41 C.17 1.3459 B.42 C.17 1.3460 B.43 C.17 1.3461 B.44 C.171.3462 B.45 C.17 1.3463 B.46 C.17 1.3464 B.47 C.17 1.3465 B.48 C.171.3466 B.49 C.17 1.3467 B.50 C.17 1.3468 B.51 C.17 1.3469 B.52 C.171.3470 B.53 C.17 1.3471 B.54 C.17 1.3472 B.55 C.17 1.3473 B.56 C.171.3474 B.57 C.17 1.3475 B.58. C.17 1.3476 B.59 C.17 1.3477 B.60 C.171.3478 B.61 C.17 1.3479 B.62 C.17 1.3480 B.63 C.17 1.3481 B.64 C.171.3482 B.65 C.17 1.3483 B.66 C.17 1.3484 B.67 C.17 1.3485 B.68 C.171.3486 B.69 C.17 1.3487 B.70 C.17 1.3488 B.71 C.17 1.3489 B.72 C.171.3490 B.73 C.17 1.3491 B.74 C.17 1.3492 B.75 C.17 1.3493 B.76 C.171.3494 B.77 C.17 1.3495 B.78 C.17 1.3496 B.79 C.17 1.3497 B.80 C.171.3498 B.81 C.17 1.3499 B.82 C.17 1.3500 B.83 C.17 1.3501 B.84 C.171.3502 B.85 C.17 1.3503 B.86 C.17 1.3504 B.87 C.17 1.3505 B.88 C.171.3506 B.89 C.17 1.3507 B.90 C.17 1.3508 B.91 C.17 1.3509 B.92 C.171.3510 B.93 C.17 1.3511 B.94 C.17 1.3512 B.95 C.17 1.3513 B.96 C.171.3514 B.97 C.17 1.3515 B.98 C.17 1.3516 B.99 C.17 1.3517 B.100 C.171.3518 B.101 C.17 1.3519 B.102 C.17 1.3520 B.103 C.17 1.3521 B.104 C.171.3522 B.105 C.17 1.3523 B.106 C.17 1.3524 B.107 C.17 1.3525 B.108 C.171.3526 B.109 C.17 1.3527 B.110 C.17 1.3528 B.111 C.17 1.3529 B.112 C.171.3530 B.113 C.17 1.3531 B.114 C.17 1.3532 B.115 C.17 1.3533 B.116 C.171.3534 B.117 C.17 1.3535 B.118 C.17 1.3536 B.119 C.17 1.3537 B.120 C.171.3538 B.121 C.17 1.3539 B.122 C.17 1.3540 B.123 C.17 1.3541 B.124 C.171.3542 B.125 C.17 1.3543 B.126 C.17 1.3544 B.127 C.17 1.3545 B.128 C.171.3546 B.129 C.17 1.3547 B.130 C.17 1.3548 B.131 C.17 1.3549 B.132 C.171.3550 B.133 C.17 1.3551 B.134 C.17 1.3552 B.135 C.17 1.3553 B.136 C.171.3554 B.137 C.17 1.3555 B.138 C.17 1.3556 B.139 C.17 1.3557 B.140 C.171.3558 B.141 C.17 1.3559 B.142 C.17 1.3560 B.143 C.17 1.3561 B.144 C.171.3562 B.145 C.17 1.3563 B.146 C.17 1.3564 B.147 C.17 1.3565 B.148 C.171.3566 B.149 C.17 1.3567 B.150 C.17 1.3568 B.151 C.17 1.3569 B.152 C.171.3570 B.153 C.17 1.3571 B.154 C.17 1.3572 B.155 C.17 1.3573 B.156 C.171.3574 B.157 C.17 1.3575 B.158 C.17 1.3576 B.159 C.17 1.3577 B.160 C.171.3578 B.161 C.17 1.3579 B.162 C.17 1.3580 B.163 C.17 1.3581 B.164 C.171.3582 B.165 C.17 1.3583 B.166 C.17 1.3584 B.167 C.17 1.3585 B.168 C.171.3586 B.169 C.17 1.3587 B.170 C.17 1.3588 B.171 C.17 1.3589 B.172 C.171.3590 B.173 C.17 1.3591 B.174 C.17 1.3592 B.175 C.17 1.3593 B.176 C.171.3594 B.177 C.17 1.3595 B.178 C.17 1.3596 B.179 C.17 1.3597 B.180 C.171.3598 B.181 C.17 1.3599 B.182 C.17 1.3600 B.183 C.17 1.3601 B.184 C.171.3602 B.185 C.17 1.3603 B.186 C.17 1.3604 B.187 C.17 1.3605 B.188 C.171.3606 B.189 C.17 1.3607 B.190 C.17 1.3608 B.191 C.17 1.3609 B.192 C.171.3610 B.193 C.17 1.3611 B.194 C.17 1.3612 B.195 C.17 1.3613 B.196 C.171.3614 B.197 C.17 1.3615 B.198 C.17 1.3616 B.199 C.17 1.3617 B.200 C.171.3618 B.201 C.17 1.3619 — C.1 1.3620 — C.2 1.3621 — C.3 1.3622 — C.41.3623 — C.5 1.3624 — C.6 1.3625 — C.7 1.3626 — C.8 1.3627 — C.9 1.3628— C.10 1.3629 — C.11 1.3630 — C.12 1.3631 — C.13 1.3632 — C.14 1.3633 —C.15 1.3634 — C.16 1.3635 — C.17 1.3636 B.202 — 1.3637 B.202 C.1 1.3638B.202 C.2 1.3639 B.202 C.3 1.3640 B.202 C.4 1.3641 B.202 C.5 1.3642B.202 C.6 1.3643 B.202 C.7 1.3644 B.202 C.8 1.3645 B.202 C.9 1.3646B.202 C.10 1.3647 B.202 C.11 1.3648 B.202 C.12 1.3649 B.202 C.13 1.3650B.202 C.14 1.3651 B.202 C.15 1.3652 B.202 C.16 1.3653 B.202 C.17

The specific number for each single composition is deductible asfollows: Composition 1.200 for example comprises the uracilpyridineI.a.339 and cinmethylin (B.200) (see table 1, entry 1.200; as well astable B, entry B.200).

Composition 2.200 for example comprises the uracilpyridine I.a.109 (seethe definition for compositions 2.1 to 2.3653, preferably 2.1 to 2.3635,below) and cinmethylin (B.200) (see table 1, entry 1.200; as well astable B, entry B.200).

Composition 7.200 for example comprises imazapyr (B.35) (see thedefinition for compositions 7.1 to 7.3653, preferably 7.1 to 7.3635,below), the uracilpyridine I.a.339 and cinmethylin (B.200) (see table 1,entry 1.200; as well as table B, entry B.200).

Also especially preferred are compositions 2.1 to 2.3653, more preferred2.1. to 2.3635, which differ from the corresponding compositions 1.1 to1.3653, more preferred 1.1 to 1.3635, only in that they comprise as theactive compound A the uracilpyridine of formula (I.a.109).

Also especially preferred are compositions 3.1 to 3.3653, more preferred3.1. to 3.3635, which differ from the corresponding compositions 1.1 to1.3653, more preferred 1.1 to 1.3635, only in that they additionallycomprise B.2 as further herbicide B.

Also especially preferred are compositions 4.1 to 4.3653, more preferred4.1. to 4.3635, which differ from the corresponding compositions 1.1 to1.3653, more preferred 1.1 to 1.3635, only in that they additionallycomprise B.8 as further herbicide B.

Also especially preferred are compositions 5.1 to 5.3653, more preferred5.1. to 5.3635, which differ from the corresponding compositions 1.1 to1.3653, more preferred 1.1 to 1.3635, only in that they additionallycomprise B.30 as further herbicide B.

Also especially preferred are compositions 6.1 to 6.3653, more preferred6.1. to 6.3635, which differ from the corresponding compositions 1.1 to1.3653, more preferred 1.1 to 1.3635, only in that they additionallycomprise B.32 as further herbicide B.

Also especially preferred are compositions 7.1 to 7.3653, more preferred7.1. to 7.3635, which differ from the corresponding compositions 1.1 to1.3653, more preferred 1.1 to 1.3635, only in that they additionallycomprise B.35 as further herbicide B.

Also especially preferred are compositions 8.1 to 8.3653, more preferred8.1. to 8.3635, which differ from the corresponding compositions 1.1 to1.3653, more preferred 1.1 to 1.3635, only in that they additionallycomprise B.38 as further herbicide B.

Also especially preferred are compositions 9.1 to 9.3653, more preferred9.1. to 9.3635, which differ from the corresponding compositions 1.1 to1.3653, more preferred 1.1 to 1.3635, only in that they additionallycomprise B.40 as further herbicide B.

Also especially preferred are compositions 10.1 to 10.3653, morepreferred 10.1. to 10.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.51 as further herbicide B.

Also especially preferred are compositions 11.1 to 11.3653, morepreferred 11.1. to 11.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.55 as further herbicide B.

Also especially preferred are compositions 12.1 to 12.3653, morepreferred 12.1. to 12.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.56 as further herbicide B.

Also especially preferred are compositions 13.1 to 13.3653, morepreferred 13.1. to 13.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.64 as further herbicide B.

Also especially preferred are compositions 14.1 to 14.3653, morepreferred 14.1. to 14.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.66 as further herbicide B.

Also especially preferred are compositions 15.1 to 15.3653, morepreferred 15.1. to 15.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.67 as further herbicide B.

Also especially preferred are compositions 16.1 to 16.3653, morepreferred 16.1. to 16.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.68 as further herbicide B.

Also especially preferred are compositions 17.1 to 17.3653, morepreferred 17.1. to 17.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.69 as further herbicide B.

Also especially preferred are compositions 18.1 to 18.3653, morepreferred 18.1. to 18.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.73 as further herbicide B.

Also especially preferred are compositions 19.1 to 19.3653, morepreferred 19.1. to 19.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.76 as further herbicide B.

Also especially preferred are compositions 20.1 to 20.3653, morepreferred 20.1. to 20.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.81 as further herbicide B.

Also especially preferred are compositions 21.1 to 21.3653, morepreferred 21.1. to 21.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.82 as further herbicide B.

Also especially preferred are compositions 22.1 to 22.3653, morepreferred 22.1. to 22.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.85 as further herbicide B.

Also especially preferred are compositions 23.1 to 23.3653, morepreferred 23.1. to 23.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.88 as further herbicide B.

Also especially preferred are compositions 24.1 to 24.3653, morepreferred 24.1. to 24.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.89 as further herbicide B.

Also especially preferred are compositions 25.1 to 25.3653, morepreferred 25.1. to 25.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.94 as further herbicide B.

Also especially preferred are compositions 26.1 to 26.3653, morepreferred 26.1. to 26.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.95 as further herbicide B.

Also especially preferred are compositions 27.1 to 27.3653, morepreferred 27.1. to 27.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.98 as further herbicide B.

Also especially preferred are compositions 28.1 to 28.3653, morepreferred 28.1. to 28.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.100 as further herbicide B.

Also especially preferred are compositions 29.1 to 29.3653, morepreferred 29.1. to 29.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.103 as further herbicide B.

Also especially preferred are compositions 30.1 to 30.3653, morepreferred 30.1. to 30.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.103 and B.67 as further herbicides B.

Also especially preferred are compositions 31.1 to 31.3653, morepreferred 31.1. to 31.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.103 and B.76 as further herbicides B.

Also especially preferred are compositions 32.1 to 32.3653, morepreferred 32.1. to 32.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.103 and B.82 as further herbicides B.

Also especially preferred are compositions 33.1 to 33.3653, morepreferred 33.1. to 33.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.104 as further herbicide B.

Also especially preferred are compositions 34.1 to 34.3653, morepreferred 34.1. to 34.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.104 and B.67 as further herbicides B.

Also especially preferred are compositions 35.1 to 35.3653, morepreferred 35.1. to 35.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.104 and B.76 as further herbicides B.

Also especially preferred are compositions 36.1 to 36.3653, morepreferred 36.1. to 36.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.104 and B.82 as further herbicides B.

Also especially preferred are compositions 37.1 to 37.3653, morepreferred 37.1. to 37.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.106 as further herbicide B.

Also especially preferred are compositions 38.1 to 38.3653, morepreferred 38.1. to 38.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.107 as further herbicide B.

Also especially preferred are compositions 39.1 to 39.3653, morepreferred 39.1. to 39.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B. 107 and B.67 as further herbicides B.

Also especially preferred are compositions 40.1 to 40.3653, morepreferred 40.1. to 40.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B. 107 and B.76 as further herbicides B.

Also especially preferred are compositions 41.1 to 41.3653, morepreferred 41.1. to 41.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B. 107 and B.82 as further herbicides B.

Also especially preferred are compositions 42.1 to 42.3653, morepreferred 42.1. to 42.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.109 as further herbicide B.

Also especially preferred are compositions 43.1 to 43.3653, morepreferred 43.1. to 43.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.111 as further herbicide B.

Also especially preferred are compositions 44.1 to 44.3653, morepreferred 44.1. to 44.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.111 and B.67 as further herbicides B.

Also especially preferred are compositions 45.1 to 45.3653, morepreferred 45.1. to 45.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.111 and B.76 as further herbicides B.

Also especially preferred are compositions 46.1 to 46.3653, morepreferred 46.1. to 46.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.111 and B.82 as further herbicides B.

Also especially preferred are compositions 47.1 to 47.3653, morepreferred 47.1. to 47.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B. 116 as further herbicide B.

Also especially preferred are compositions 48.1 to 48.3653, morepreferred 48.1. to 48.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.116 and B.67 as further herbicides B.

Also especially preferred are compositions 49.1 to 49.3653, morepreferred 49.1. to 49.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.116 and B.94 as further herbicides B.

Also especially preferred are compositions 50.1 to 50.3653, morepreferred 50.1. to 50.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.116 and B.103 as further herbicides B.

Also especially preferred are compositions 51.1 to 51.3653, morepreferred 51.1. to 51.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.116 and B.128 as further herbicides B.

Also especially preferred are compositions 52.1 to 52.3653, morepreferred 52.1. to 52.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.116 and B.104 as further herbicides B.

Also especially preferred are compositions 53.1 to 53.3653, morepreferred 53.1. to 53.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.116 and B.107 as further herbicides B.

Also especially preferred are compositions 54.1 to 54.3653, morepreferred 54.1. to 54.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.116 and B.111 as further herbicides B.

Also especially preferred are compositions 55.1 to 55.3653, morepreferred 55.1. to 55.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.122 as further herbicide B.

Also especially preferred are compositions 56.1 to 56.3653, morepreferred 56.1. to 56.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.126 as further herbicide B.

Also especially preferred are compositions 57.1 to 57.3653, morepreferred 57.1. to 57.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.128 as further herbicide B.

Also especially preferred are compositions 58.1 to 58.3653, morepreferred 58.1. to 58.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.131 as further herbicide B.

Also especially preferred are compositions 59.1 to 59.3653, morepreferred 59.1. to 59.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.132 as further herbicide B.

Also especially preferred are compositions 60.1 to 60.3653, morepreferred 60.1. to 60.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.133 as further herbicide B.

Also especially preferred are compositions 61.1 to 61.3653, morepreferred 61.1. to 61.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.135 as further herbicide B.

Also especially preferred are compositions 62.1 to 62.3653, morepreferred 62.1. to 62.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.137 as further herbicide B.

Also especially preferred are compositions 63.1 to 63.3653, morepreferred 63.1. to 63.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 11.1 to 1.3635, only in thatthey additionally comprise B.138 as further herbicide B.

Also especially preferred are compositions 64.1 to 64.3653, morepreferred 64.1. to 64.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.140 as further herbicide B.

Also especially preferred are compositions 65.1 to 65.3653, morepreferred 65.1. to 65.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.145 as further herbicide B.

Also especially preferred are compositions 66.1 to 66.3653, morepreferred 66.1. to 66.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.153 as further herbicide B.

Also especially preferred are compositions 67.1 to 67.3653, morepreferred 67.1. to 67.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.156 as further herbicide B.

Also especially preferred are compositions 68.1 to 68.3653, morepreferred 68.1. to 68.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.171 as further herbicide B.

Also especially preferred are compositions 69.1 to 69.3653, morepreferred 69.1. to 69.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey additionally comprise B.174 as further herbicide B.

Also especially preferred are compositions 70.1 to 70.3653, morepreferred 70.1. to 70.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.a.115).

Also especially preferred are compositions 71.1 to 71.3653, morepreferred 71.1. to 71.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.a.255).

Also especially preferred are compositions 72.1 to 72.3653, morepreferred 72.1. to 72.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.a.277).

Also especially preferred are compositions 73.1 to 73.3653, morepreferred 73.1. to 73.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.a.283).

Also especially preferred are compositions 74.1 to 74.3653, morepreferred 74.1. to 74.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.a.87).

Also especially preferred are compositions 75.1 to 75.3653, morepreferred 75.1. to 75.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.a.361).

Also especially preferred are compositions 76.1 to 76.3653, morepreferred 76.1. to 76.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.a.367).

Also especially preferred are compositions 77.1 to 77.3653, morepreferred 77.1. to 77.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.87).

Also especially preferred are compositions 78.1 to 78.3653, morepreferred 78.1. to 78.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.109).

Also especially preferred are compositions 79.1 to 79.3653, morepreferred 79.1. to 79.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.115).

Also especially preferred are compositions 80.1 to 80.3653, morepreferred 80.1. to 80.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.255).

Also especially preferred are compositions 81.1 to 81.3653, morepreferred 81.1. to 81.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.277).

Also especially preferred are compositions 82.1 to 82.3653, morepreferred 82.1. to 82.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.283).

Also especially preferred are compositions 83.1 to 83.3653, morepreferred 83.1. to 83.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339).

Also especially preferred are compositions 84.1 to 84.3653, morepreferred 84.1. to 84.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.361).

Also especially preferred are compositions 85.1 to 85.3653, morepreferred 85.1. to 85.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.367).

Also especially preferred are compositions 86.1 to 86.3653, morepreferred 86.1. to 86.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in theycomprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.2 as further herbicide B.

Also especially preferred are compositions 87.1 to 87.3653, morepreferred 87.1. to 87.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.8 as further herbicide B.

Also especially preferred are compositions 88.1 to 88.3653, morepreferred 88.1. to 88.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.30 as further herbicide B.

Also especially preferred are compositions 89.1 to 89.3653, morepreferred 89.1. to 89.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.32 as further herbicide B.

Also especially preferred are compositions 90.1 to 90.3653, morepreferred 90.1. to 90.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.35 as further herbicide B.

Also especially preferred are compositions 91.1 to 91.3653, morepreferred 91.1. to 91.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.38 as further herbicide B.

Also especially preferred are compositions 92.1 to 92.3653, morepreferred 92.1. to 92.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.40 as further herbicide B.

Also especially preferred are compositions 93.1 to 93.3653, morepreferred 93.1. to 93.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.51 as further herbicide B.

Also especially preferred are compositions 94.1 to 94.3653, morepreferred 94.1. to 94.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.55 as further herbicide B.

Also especially preferred are compositions 95.1 to 95.3653, morepreferred 95.1. to 95.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.56 as further herbicide B.

Also especially preferred are compositions 96.1 to 96.3653, morepreferred 96.1. to 96.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.64 as further herbicide B.

Also especially preferred are compositions 97.1 to 97.3653, morepreferred 97.1. to 97.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.66 as further herbicide B.

Also especially preferred are compositions 98.1 to 98.3653, morepreferred 98.1. to 98.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.67 as further herbicide B.

Also especially preferred are compositions 99.1 to 99.3653, morepreferred 99.1. to 99.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.68 as further herbicide B.

Also especially preferred are compositions 100.1 to 100.3653, morepreferred 100.1. to 100.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.69 as further herbicide B.

Also especially preferred are compositions 101.1 to 101.3653, morepreferred 101.1. to 101.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.73 as further herbicide B.

Also especially preferred are compositions 102.1 to 102.3653, morepreferred 102.1. to 102.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635 only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.76 as further herbicide B.

Also especially preferred are compositions 103.1 to 103.3653, morepreferred 103.1. to 103.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.81 as further herbicide B.

Also especially preferred are compositions 104.1 to 104.3653, morepreferred 104.1. to 104.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.82 as further herbicide B.

Also especially preferred are compositions 105.1 to 105.3653, morepreferred 105.1. to 105.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.85 as further herbicide B.

Also especially preferred are compositions 106.1 to 106.3653, morepreferred 106.1. to 106.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.88 as further herbicide B.

Also especially preferred are compositions 107.1 to 107.3653, morepreferred 107.1. to 107.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.89 as further herbicide B.

Also especially preferred are compositions 108.1 to 108.3653, morepreferred 108.1. to 108.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.94 as further herbicide B.

Also especially preferred are compositions 191.1 to 109.3653, morepreferred 109.1. to 109.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.95 as further herbicide B.

Also especially preferred are compositions 110.1 to 110.3653, morepreferred 110.1. to 110.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.98 as further herbicide B.

Also especially preferred are compositions 111.1 to 111.3653, morepreferred 111.1. to 111.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.100 as further herbicide B.

Also especially preferred are compositions 112.1 to 112.3653, morepreferred 112.1. to 112.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.103 as further herbicide B.

Also especially preferred are compositions 113.1 to 113.3653, morepreferred 113.1. to 113.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.103 and B.67 as further herbicidesB.

Also especially preferred are compositions 114.1 to 114.3653, morepreferred 114.1. to 114.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.103 and B.76 as further herbicidesB.

Also especially preferred are compositions 115.1 to 115.3653, morepreferred 115.1. to 115.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.103 and B.82 as further herbicidesB.

Also especially preferred are compositions 116.1 to 116.3653, morepreferred 116.1. to 116.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.104 as further herbicide B.

Also especially preferred are compositions 117.1 to 117.3653, morepreferred 117.1. to 117.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.104 and B.67 as further herbicidesB.

Also especially preferred are compositions 118.1 to 118.3653, morepreferred 118.1. to 118.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.104 and B.76 as further herbicidesB.

Also especially preferred are compositions 119.1 to 119.3653, morepreferred 119.1. to 119.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.104 and B.82 as further herbicidesB.

Also especially preferred are compositions 120.1 to 120.3653, morepreferred 120.1. to 120.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.106 as further herbicide B.

Also especially preferred are compositions 121.1 to 121.3653, morepreferred 121.1. to 121.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.107 as further herbicide B.

Also especially preferred are compositions 122.1 to 122.3653, morepreferred 122.1. to 122.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B. 107 and B.67 as furtherherbicides B.

Also especially preferred are compositions 123.1 to 123.3653, morepreferred 123.1. to 123.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B. 107 and B.76 as furtherherbicides B.

Also especially preferred are compositions 124.1 to 124.3653, morepreferred 124.1. to 124.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B. 107 and B.82 as furtherherbicides B.

Also especially preferred are compositions 125.1 to 125.3653, morepreferred 125.1. to 125.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.109 as further herbicide B.

Also especially preferred are compositions 126.1 to 126.3653, morepreferred 126.1. to 126.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.111 as further herbicide B.

Also especially preferred are compositions 127.1 to 127.3653, morepreferred 127.1. to 127.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.111 and B.67 as further herbicidesB.

Also especially preferred are compositions 128.1 to 128.3653, morepreferred 128.1. to 128.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.111 and B.76 as further herbicidesB.

Also especially preferred are compositions 129.1 to 129.3653, morepreferred 129.1. to 129.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.111 and B.82 as further herbicidesB.

Also especially preferred are compositions 130.1 to 130.3653, morepreferred 130.1. to 130.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B. 116 as further herbicide B.

Also especially preferred are compositions 131.1 to 131.3653, morepreferred 131.1. to 131.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.116 and B.67 as further herbicidesB.

Also especially preferred are compositions 132.1 to 132.3653, morepreferred 132.1. to 132.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.116 and B.94 as further herbicidesB.

Also especially preferred are compositions 133.1 to 133.3653, morepreferred 133.1. to 133.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.116 and B.103 as furtherherbicides B.

Also especially preferred are compositions 134.1 to 134.3653, morepreferred 134.1. to 134.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.116 and B.128 as furtherherbicides B.

Also especially preferred are compositions 135.1 to 135.3653, morepreferred 135.1. to 135.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.116 and B.104 as furtherherbicides B.

Also especially preferred are compositions 136.1 to 136.3653, morepreferred 136.1. to 136.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.116 and B.107 as furtherherbicides B.

Also especially preferred are compositions 137.1 to 137.3653, morepreferred 137.1. to 137.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.116 and B.111 as furtherherbicides B.

Also especially preferred are compositions 138.1 to 138.3653, morepreferred 138.1. to 138.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.122 as further herbicide B.

Also especially preferred are compositions 139.1 to 139.3653, morepreferred 139.1. to 139.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.126 as further herbicide B.

Also especially preferred are compositions 140.1 to 140.3653, morepreferred 140.1. to 140.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.128 as further herbicide B.

Also especially preferred are compositions 141.1 to 141.3653, morepreferred 141.1. to 141.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.131 as further herbicide B.

Also especially preferred are compositions 142.1 to 142.3653, morepreferred 142.1. to 142.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.132 as further herbicide B.

Also especially preferred are compositions 143.1 to 143.3653, morepreferred 143.1. to 143.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.133 as further herbicide B.

Also especially preferred are compositions 144.1 to 144.3653, morepreferred 144.1. to 144.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.135 as further herbicide B.

Also especially preferred are compositions 145.1 to 145.3653, morepreferred 145.1. to 145.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.137 as further herbicide B.

Also especially preferred are compositions 146.1 to 146.3653, morepreferred 146.1. to 146.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.138 as further herbicide B.

Also especially preferred are compositions 147.1 to 147.3653, morepreferred 147.1. to 147.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.140 as further herbicide B.

Also especially preferred are compositions 148.1 to 148.3653, morepreferred 148.1. to 148.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.145 as further herbicide B.

Also especially preferred are compositions 149.1 to 149.3653, morepreferred 149.1. to 149.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.153 as further herbicide B.

Also especially preferred are compositions 150.1 to 150.3653, morepreferred 150.1. to 150.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.156 as further herbicide B.

Also especially preferred are compositions 151.1 to 151.3653, morepreferred 151.1. to 151.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.171 as further herbicide B.

Also especially preferred are compositions 152.1 to 152.3653, morepreferred 152.1. to 152.3635, which differ from the correspondingcompositions 1.1 to 1.3653, more preferred 1.1 to 1.3635, only in thatthey comprise as the active compound A the uracilpyridine of formula(I.h.339) and additionally comprise B.174 as further herbicide B.

It is generally preferred to use the compounds of the invention incombination with herbicides that are selective for the crop beingtreated and which complement the spectrum of weeds controlled by thesecompounds at the application rate employed. It is further generallypreferred to apply the compounds of the invention and othercomplementary herbicides at the same time, either as a combinationformulation or as a tank mix.

It is recognized that the polynucleotide molecules and polypeptides ofthe invention encompass polypeptides comprising an amino acid sequencethat is sufficiently identical to the amino acid sequences set forth inSEQ ID Nos: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 265, 266,267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280,281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294,295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308,309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322,323, 324, 325, 326, 327328, 329, 330, 331, 332, 333, 334, 335, 336, 337,338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351,352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365,366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379,380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393,394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407,408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421,422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435,436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449,450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463,464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477,478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491,492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505,506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519,520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533,534, 535, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546, 547,548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561,562, 563, 564, 565, 577, 579, 581, 583, 585, 587, 589, 591, 593, 595,597, 599, 601, 603, 605, 607, 609, 611, 613, 615, 617, 619, 621, 623,625, 627, or 637. The term “sufficiently identical” is used herein torefer to a first amino acid or nucleotide sequence that contains asufficient or minimum number of identical or equivalent (e.g., with asimilar side chain) amino acid residues or nucleotides to a second aminoacid or nucleotide sequence such that the first and second amino acid ornucleotide sequences have a common structural domain and/or commonfunctional activity.

Generally, “sequence identity” refers to the extent to which twooptimally aligned DNA or amino acid sequences are invariant throughout awindow of alignment of components, e.g., nucleotides or amino acids. An“identity fraction” for aligned segments of a test sequence and areference sequence is the number of identical components that are sharedby the two aligned sequences divided by the total number of componentsin reference sequence segment, i.e., the entire reference sequence or asmaller defined part of the reference sequence. “Percent identity” isthe identity fraction times 100. Optimal alignment of sequences foraligning a comparison window are well known to those skilled in the artand may be conducted by tools such as the local homology algorithm ofSmith and Waterman, the homology alignment algorithm of Needleman andWunsch, the search for similarity method of Pearson and Lipman, andpreferably by computerized implementations of these algorithms such asGAP, BESTFIT, FASTA, and TFASTA available as part of the GCG. WisconsinPackage. (Accelrys Inc. Burlington, Mass.)

Polynucleotides and Oligonucleotides

By an “isolated polynucleotide”, including DNA, RNA, or a combination ofthese, single or double stranded, in the sense or antisense orientationor a combination of both, dsRNA or otherwise, we mean a polynucleotidewhich is at least partially separated from the polynucleotide sequenceswith which it is associated or linked in its native state. That meansother nucleic acid molecules are present in an amount less than 5% basedon weight of the amount of the desired nucleic acid, preferably lessthan 2% by weight, more preferably less than 1% by weight, mostpreferably less than 0.5% by weight. Preferably, an “isolated” nucleicacid is free of some of the sequences that naturally flank the nucleicacid (i.e., sequences located at the 5′ and 3′ ends of the nucleic acid)in the genomic DNA of the organism from which the nucleic acid isderived. For example, in various embodiments, the isolated herbicideresistance and/or tolerance related protein encoding nucleic acidmolecule can contain less than about 5 kb, 4 kb, 3 kb, 2 kb, 1 kb, 0.5kb or 0.1 kb of nucleotide sequences which naturally flank the nucleicacid molecule in genomic DNA of the cell from which the nucleic acid isderived. Moreover, an “isolated” nucleic acid molecule, such as a cDNAmolecule, can be free from some of the other cellular material withwhich it is naturally associated, or culture medium when produced byrecombinant techniques, or chemical precursors or other chemicals whenchemically synthesized. Preferably, the isolated polynucleotide is atleast 60% free, preferably at least 75% free, and most preferably atleast 90% free from other components with which they are naturallyassociated. As the skilled addressee would be aware, an isolatedpolynucleotide can be an exogenous polynucleotide present in, forexample, a transgenic organism which does not naturally comprise thepolynucleotide. Furthermore, the terms “polynucleotide(s)”, “nucleicacid sequence(s)”, “nucleotide sequence(s)”, “nucleic acid(s)”, “nucleicacid molecule” are used interchangeably herein and refer to nucleotides,either ribonucleotides or deoxyribonucleotides or a combination of both,in a polymeric unbranched form of any length.

The term “mutated PPO nucleic acid” refers to a PPO nucleic acid havinga sequence that is mutated from a wild-type PPO nucleic acid, such ase.g. SEQ ID NO: 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128,624, 626, or 650, or homologues, paralogues and orthologues thereof; andthat confers increased uracilpyridine herbicide tolerance to a plant inwhich it is expressed. Furthermore, the term “mutated protoporphyrinogenoxidase (mutated PPO)” refers to the replacement of an amino acid of thewild-type primary sequences SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28,29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46,47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64,65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82,83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100,101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114,115, 116, 117, 577, 579, 581, 583, 585, 587, 589, 591, 593, 595, 597,599, 601, 603, 605, 607, 609, 611, 613, 615, 617, 619, 621, 623, 625,627, or 637, or a variant, a derivative, a homologue, an orthologue, orparalogue thereof, with another amino acid. The expression “mutatedamino acid” will be used below to designate the amino acid which isreplaced by another amino acid, thereby designating the site of themutation in the primary sequence of the protein.

In a preferred embodiment, the PPO nucleotide sequence encoding amutated PPO comprises the sequence of SEQ ID NO: 118, 119, 120, 121,122, 123, 124, 125, 126, 127, 128, 624, 626, or 650, or a variant orderivative thereof.

Furthermore, it will be understood by the person skilled in the art thatthe PPO nucleotide sequences encompasse homologues, paralogues andorthologues of SEQ ID NO: 118, 119, 120, 121, 122, 123, 124, 125, 126,127, 128, 624, 626, or 650, as defined hereinafter.

The term “variant” with respect to a sequence (e.g., a polypeptide ornucleic acid sequence such as—for example—a transcription regulatingnucleotide sequence of the invention) is intended to mean substantiallysimilar sequences. For nucleotide sequences comprising an open readingframe, variants include those sequences that, because of the degeneracyof the genetic code, encode the identical amino acid sequence of thenative protein. Naturally occurring allelic variants such as these canbe identified with the use of well-known molecular biology techniques,as, for example, with polymerase chain reaction (PCR) and hybridizationtechniques. Variant nucleotide sequences also include syntheticallyderived nucleotide sequences, such as those generated, for example, byusing site-directed mutagenesis and for open reading frames, encode thenative protein, as well as those that encode a polypeptide having aminoacid substitutions relative to the native protein, e.g. the mutated PPOaccording to the present invention as disclosed herein.

Generally, nucleotide sequence variants of the invention will have atleast 30, 40, 50, 60, to 70%, e.g., preferably 71%, 72%, 73%, 74%, 75%,76%, 77%, 78%, to 79%, generally at least 80%, e.g., 81%-84%, at least85%, e.g., 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%,to 98% and 99% nucleotide “sequence identity” to the nucleotide sequenceencoding a polypeptide of SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29,30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47,48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65,66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83,84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100,101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114,115, 116, 117, 577, 579, 581, 583, 585, 587, 589, 591, 593, 595, 597,599, 601, 603, 605, 607, 609, 611, 613, 615, 617, 619, 621, 623, 625,627, 637, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276,277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290,291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304,305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318,319, 320, 321, 322, 323, 324, 325, 326, 327328, 329, 330, 331, 332, 333,334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347,348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361,362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375,376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389,390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403,404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417,418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431,432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445,446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459,460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473,474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487,488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501,502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515,516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529,530, 531, 532, 533, 534, 535, 536, 537, 538, 539, 540, 541, 542, 543,544, 545, 546, 547, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557,558, 559, 560, 561, 562, 563, 564, or 565.

The % identity of a polynucleotide is determined by GAP (Needleman andWunsch, 1970) analysis (GCG program) with a gap creation penalty=5, anda gap extension penalty=0.3. Unless stated otherwise, the query sequenceis at least 45 nucleotides in length, and the GAP analysis aligns thetwo sequences over a region of at least 45 nucleotides. Preferably, thequery sequence is at least 150 nucleotides in length, and the GAPanalysis aligns the two sequences over a region of at least 150nucleotides. More preferably, the query sequence is at least 300nucleotides in length and the GAP analysis aligns the two sequences overa region of at least 300 nucleotides. Even more preferably, the GAPanalysis aligns the two sequences over their entire length.

Polypeptides

By “substantially purified polypeptide” or “purified” a polypeptide ismeant that has been separated from one or more lipids, nucleic acids,other polypeptides, or other contaminating molecules with which it isassociated in its native state. It is preferred that the substantiallypurified polypeptide is at least 60% free, more preferably at least 75%free, and more preferably at least 90% free from other components withwhich it is naturally associated. As the skilled addressee willappreciate, the purified polypeptide can be a recombinantly producedpolypeptide. The terms “polypeptide” and “protein” are generally usedinterchangeably and refer to a single polypeptide chain which may or maynot be modified by addition of non-amino acid groups. It would beunderstood that such polypeptide chains may associate with otherpolypeptides or proteins or other molecules such as co-factors. Theterms “proteins” and “polypeptides” as used herein also includevariants, mutants, modifications, analogous and/or derivatives of thepolypeptides of the invention as described herein.

The % identity of a polypeptide is determined by GAP (Needleman andWunsch, 1970) analysis (GCG program) with a gap creation penalty=5, anda gap extension penalty=0.3. The query sequence is at least 25 aminoacids in length, and the GAP analysis aligns the two sequences over aregion of at least 25 amino acids. More preferably, the query sequenceis at least 50 amino acids in length, and the GAP analysis aligns thetwo sequences over a region of at least 50 amino acids. More preferably,the query sequence is at least 100 amino acids in length and the GAPanalysis aligns the two sequences over a region of at least 100 aminoacids. Even more preferably, the query sequence is at least 250 aminoacids in length and the GAP analysis aligns the two sequences over aregion of at least 250 amino acids. Even more preferably, the GAPanalysis aligns the two sequences over their entire length.

With regard to a defined polypeptide, it will be appreciated that %identity figures higher than those provided above will encompasspreferred embodiments. Thus, where applicable, in light of the minimum %identity figures, it is preferred that the PPO polypeptide of theinvention comprises an amino acid sequence which is at least 40%, morepreferably at least 45%, more preferably at least 50%, more preferablyat least 55%, more preferably at least 60%, more preferably at least65%, more preferably at least 70%, more preferably at least 75%, morepreferably at least 80%, more preferably at least 85%, more preferablyat least 90%, more preferably at least 91%, more preferably at least92%, more preferably at least 93%, more preferably at least 94%, morepreferably at least 95%, more preferably at least 96%, more preferablyat least 97%, more preferably at least 98%, more preferably at least99%, more preferably at least 99.1%, more preferably at least 99.2%,more preferably at least 99.3%, more preferably at least 99.4%, morepreferably at least 99.5%, more preferably at least 99.6%, morepreferably at least 99.7%, more preferably at least 99.8%, and even morepreferably at least 99.9% identical to SEQ ID NO: 1, 2, 3, 4, 5, 6, 7,8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25,26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43,44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61,62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79,80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97,98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112,113, 114, 115, 116, 117, 577, 579, 581, 583, 585, 587, 589, 591, 593,595, 597, 599, 601, 603, 605, 607, 609, 611, 613, 615, 617, 619, 621,623, 625, 627, 637, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274,275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288,289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302,303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316,317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327328, 329, 330, 331,332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345,346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359,360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373,374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387,388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401,402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415,416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429,430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443,444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457,458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471,472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485,486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499,500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513,514, 515, 516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526, 527,528, 529, 530, 531, 532, 533, 534, 535, 536, 537, 538, 539, 540, 541,542, 543, 544, 545, 546, 547, 548, 549, 550, 551, 552, 553, 554, 555,556, 557, 558, 559, 560, 561, 562, 563, 564,or 565.

By “variant” polypeptide is intended a polypeptide derived from theprotein of SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15,16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33,34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51,52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69,70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87,88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104,105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577,579, 581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605,607, 609, 611, 613, 615, 617, 619, 621, 623, 625, 627, 637, 265, 266,267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280,281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294,295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308,309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322,323, 324, 325, 326, 327328, 329, 330, 331, 332, 333, 334, 335, 336, 337,338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351,352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365,366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379,380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393,394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407,408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421,422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435,436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449,450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463,464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477,478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491,492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505,506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519,520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533,534, 535, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546, 547,548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561,562, 563, 564, or 565, by deletion (so-called truncation) or addition ofone or more amino acids to the N-terminal and/or C-terminal end of thenative protein; deletion or addition of one or more amino acids at oneor more sites in the native protein; or substitution of one or moreamino acids at one or more sites in the native protein. Such variantsmay result from, for example, genetic polymorphism or from humanmanipulation. Methods for such manipulations are generally known in theart.

“Derivatives” of a protein encompass peptides, oligopeptides,polypeptides, proteins and enzymes having amino acid substitutions,deletions and/or insertions relative to the unmodified protein inquestion and having similar biological and functional activity as theunmodified protein from which they are derived.

“Homologues” of a protein encompass peptides, oligopeptides,polypeptides, proteins and enzymes having amino acid substitutions,deletions and/or insertions relative to the unmodified protein inquestion and having similar biological and functional activity as theunmodified protein from which they are derived.

A deletion refers to removal of one or more amino acids from a protein.

An insertion refers to one or more amino acid residues being introducedinto a predetermined site in a protein. Insertions may compriseN-terminal and/or C-terminal fusions as well as intra-sequenceinsertions of single or multiple amino acids. Generally, insertionswithin the amino acid sequence will be smaller than N- or C-terminalfusions, of the order of about 1 to 10 residues. Examples of N- orC-terminal fusion proteins or peptides include the binding domain oractivation domain of a transcriptional activator as used in the yeasttwo-hybrid system, phage coat proteins, (histidine)-6-tag, glutathioneS-transferase-tag, protein A, maltose-binding protein, dihydrofolatereductase, Tag•100 epitope, c-myc epitope, FLAG®-epitope, lacZ, CMP(calmodulin-binding peptide), HA epitope, protein C epitope and VSVepitope.

A substitution refers to replacement of amino acids of the protein withother amino acids having similar properties (such as similarhydrophobicity, hydrophilicity, antigenicity, propensity to form orbreak a-helical structures or β-sheet structures). Amino acidsubstitutions are typically of single residues, but may be clustereddepending upon functional constraints placed upon the polypeptide andmay range from 1 to 10 amino acids; insertions will usually be of theorder of about 1 to 10 amino acid residues. The amino acid substitutionsare preferably conservative amino acid substitutions. Conservativesubstitution tables are well known in the art (see for example Creighton(1984) Proteins. W.H. Freeman and Company (Eds).

TABLE 1 Examples of conserved amino acid substitutions ConservativeResidue Substitutions Ala Ser Arg Lys Asn Gln; His Asp Glu Gln Asn CysSer Glu Asp Gly Pro His Asn; Gln Ile Leu, Val Leu Ile; Val Lys Arg; GlnMet Leu; Ile Phe Met; Leu; Tyr Ser Thr; Gly Thr Ser; Val Trp Tyr TyrTrp; Phe Val Ile; Leu

Amino acid substitutions, deletions and/or insertions may readily bemade using peptide synthetic techniques well known in the art, such assolid phase peptide synthesis and the like, or by recombinant DNAmanipulation. Methods for the manipulation of DNA sequences to producesubstitution, insertion or deletion variants of a protein are well knownin the art. For example, techniques for making substitution mutations atpredetermined sites in DNA are well known to those skilled in the artand include M13 mutagenesis, T7-Gen in vitro mutagenesis (USB,Cleveland, Ohio), QuickChange Site Directed mutagenesis (Stratagene, SanDiego, Calif.), PCR-mediated site-directed mutagenesis or othersite-directed mutagenesis protocols.

“Derivatives” further include peptides, oligopeptides, polypeptideswhich may, compared to the amino acid sequence of thenaturally-occurring form of the protein, such as the protein ofinterest, comprise substitutions of amino acids with non-naturallyoccurring amino acid residues, or additions of non-naturally occurringamino acid residues. “Derivatives” of a protein also encompass peptides,oligopeptides, polypeptides which comprise naturally occurring altered(glycosylated, acylated, prenylated, phosphorylated, myristoylated,sulphated etc.) or non-naturally altered amino acid residues compared tothe amino acid sequence of a naturally-occurring form of thepolypeptide. A derivative may also comprise one or more non-amino acidsubstituents or additions compared to the amino acid sequence from whichit is derived, for example a reporter molecule or other ligand,covalently or non-covalently bound to the amino acid sequence, such as areporter molecule which is bound to facilitate its detection, andnon-naturally occurring amino acid residues relative to the amino acidsequence of a naturally-occurring protein. Furthermore, “derivatives”also include fusions of the naturally-occurring form of the protein withtagging peptides such as FLAG, HIS6 or thioredoxin (for a review oftagging peptides, see Terpe, Appl. Microbiol. Biotechnol. 60, 523-533,2003).

“Orthologues” and “paralogues” encompass evolutionary concepts used todescribe the ancestral relationships of genes. Paralogues are geneswithin the same species that have originated through duplication of anancestral gene; orthologues are genes from different organisms that haveoriginated through speciation, and are also derived from a commonancestral gene.

It is well-known in the art that paralogues and orthologues may sharedistinct domains harboring suitable amino acid residues at given sites,such as binding pockets for particular substrates or binding motifs forinteraction with other proteins.

The term “domain” refers to a set of amino acids conserved at specificpositions along an alignment of sequences of evolutionarily relatedproteins. While amino acids at other positions can vary betweenhomologues, amino acids that are highly conserved at specific positionsindicate amino acids that are likely essential in the structure,stability or function of a protein. Identified by their high degree ofconservation in aligned sequences of a family of protein homologues,they can be used as identifiers to determine if any polypeptide inquestion belongs to a previously identified polypeptide family.

The term “motif” or “consensus sequence” refers to a short conservedregion in the sequence of evolutionarily related proteins. Motifs arefrequently highly conserved parts of domains, but may also include onlypart of the domain, or be located outside of conserved domain (if all ofthe amino acids of the motif fall outside of a defined domain).Preferred motifs which are contained in the sequences of the PPOpolypeptides according to the present invention are SQ[N/K/H]KRYI,TLGTLFSS, [F/Y]TTF[V/I]GG.

Specialist databases exist for the identification of domains, forexample, SMART (Schultz et al. (1998) Proc. Natl. Acad. Sci. USA 95,5857-5864; Letunic et al. (2002) Nucleic Acids Res 30, 242-244),InterPro (Mulder et al., (2003) Nucl. Acids. Res. 31, 315-318), Prosite(Bucher and Bairoch (1994), A generalized profile syntax forbiomolecular sequences motifs and its function in automatic sequenceinterpretation. (In) ISMB-94; Proceedings 2nd International Conferenceon Intelligent Systems for Molecular Biology. Altman R., Brutlag D.,Karp P., Lathrop R., Searls D., Eds., pp 53-61, AAAI Press, Menlo Park;Hulo et al., Nucl. Acids. Res. 32:D134-D137, (2004)), or Pfam (Batemanet al., Nucleic Acids Research 30(1): 276-280 (2002)). A set of toolsfor in silico analysis of protein sequences is available on the ExPASyproteomics server (Swiss Institute of Bioinformatics (Gasteiger et al.,ExPASy: the proteomics server for in-depth protein knowledge andanalysis, Nucleic Acids Res. 31:3784-3788(2003)). Domains or motifs mayalso be identified using routine techniques, such as by sequencealignment.

Methods for the alignment of sequences for comparison are well known inthe art, such methods include GAP, BESTFIT, BLAST, FASTA and TFASTA. GAPuses the algorithm of Needleman and Wunsch ((1970) J Mol Biol 48:443-453) to find the global (i.e. spanning the complete sequences)alignment of two sequences that maximizes the number of matches andminimizes the number of gaps. The BLAST algorithm (Altschul et al.(1990) J Mol Biol 215: 403-10) calculates percent sequence identity andperforms a statistical analysis of the similarity between the twosequences. The software for performing BLAST analysis is publiclyavailable through the National Centre for Biotechnology Information(NCBI).

Homologues may readily be identified using, for example, the ClustalWmultiple sequence alignment algorithm (version 1.83), with the defaultpairwise alignment parameters, and a scoring method in percentage.Global percentages of similarity and identity may also be determinedusing one of the methods available in the MatGAT software package(Campanella et al., BMC Bioinformatics. 2003 Jul. 10; 4:29. MatGAT: anapplication that generates similarity/identity matrices using protein orDNA sequences.). Minor manual editing may be performed to optimisealignment between conserved motifs, as would be apparent to a personskilled in the art. Furthermore, instead of using full-length sequencesfor the identification of homologues, specific domains may also be used.The sequence identity values may be determined over the entire nucleicacid or amino acid sequence or over selected domains or conservedmotif(s), using the programs mentioned above using the defaultparameters. For local alignments, the Smith-Waterman algorithm isparticularly useful (Smith T F, Waterman M S (1981) J. Mol. Biol 147(1);195-7).

The inventors of the present invention have found that by substitutingone or more of the key amino acid residues, employing e.g. one of theabove described methods to mutate the encoding nucleic acids, theuracilpyridine herbicide tolerance or resistance could be remarkablyincreased as compared to the activity of the wild type PPO enzymes withSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637. Preferredsubstitutions of mutated PPO are those that increase the herbicidetolerance of the plant, but leave the biological activity of the oxidaseactivity substantially unaffected.

Accordingly, in another object of the present invention the key aminoacid residues of a PPO enzyme comprising SEQ ID NO: 1, 2, 3, 4, 5, 6, 7,8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25,26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43,44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61,62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79,80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97,98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112,113, 114, 115, 116, 117, 577, 579, 581, 583, 585, 587, 589, 591, 593,595, 597, 599, 601, 603, 605, 607, 609, 611, 613, 615, 617, 619, 621,623, 625, 627, or 637,a variant, derivative, orthologue, paralogue orhomologue thereof, is substituted by any other amino acid.

In one embodiment, the key amino acid residues of a PPO enzyme, avariant, derivative, orthologue, paralogue or homologue thereof, issubstituted by a conserved amino acid as depicted in Table 1.

It will be understood by the person skilled in the art that amino acidslocated in a close proximity to the positions of amino acids mentionedbelow may also be substituted. Thus, in another embodiment the variantof SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof comprises amutated PPO, wherein an amino acid 3, ±2 or ±1 amino acid positions froma key amino acid is substituted by any other amino acid.

Based on techniques well-known in the art, a highly characteristicsequence pattern can be developed, by means of which further of mutatedPPO candidates with the desired activity may be searched.

Searching for further mutated PPO candidates by applying a suitablesequence pattern would also be encompassed by the present invention. Itwill be understood by a skilled reader that the present sequence patternis not limited by the exact distances between two adjacent amino acidresidues of said pattern. Each of the distances between two neighboursin the above patterns may, for example, vary independently of each otherby up to ±10, ±5, ±3, ±2 or ±1 amino acid positions withoutsubstantially affecting the desired activity.

Furthermore, by applying the method of site directed mutagenesis, inparticular saturation mutagenes (see e.g. Schenk et al., Biospektrum03/2006, pages 277-279), the inventors of the present invention haveidentified and generated specific amino acid substitutions andcombinations thereof, which—when introduced into a plant by transformingand expressing the respective mutated PPO encoding nucleic acid—conferincreased herbicide resistance or tolerance to a uracilpyridineherbicide to said plant.

Thus, in a particularly preferred embodiment, the variant or derivativeof the mutated PPO refers to a polypeptide comprising SEQ ID NO: 1, 2,3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22,23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40,41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58,59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76,77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94,95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109,110, 111, 112, 113, 114, 115, 116, 117, or 637, comprising a singleamino acid substitution at positions depicted in the following Table 2a.

TABLE 2a-1 Single amino acid substitutions within SEQ ID NO: 1, 2, 3, 4,5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41,42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59,60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77,78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95,96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110,111, 112, 113, 114, 115, 116, 117, or 637 SEQ Mutated Mutated MutatedMutated Mutated ID Organism site 1 site 2 site 3 site 4 site 5 1Amaranthus tuberculatus R128 G210 G211 L397 F420 2 Amaranthustuberculatus R128 G210 G211 L397 F420 3 Amaranthus tuberculatus R128G210 — L396 F419 4 Amaranthus tuberculatus R128 G210 — L396 F419 5Amaranthus R128 G210 G211 L398 F421 hypochondriacus 6 Amaranthustuberculatus R98 G180 G181 L368 F391 7 Spinacia oleracea R127 G209 G210L397 F420 8 Vitis vinifera R100 G182 G183 L373 F396 9 Ricinus communisR99 A181 G182 L372 F395 10 Theobroma cacao R98 A180 G181 L370 F393 11Glycine max R98 A180 A181 L367 F390 12 Prunus persica R96 A175 G176 L366F389 13 Medicago truncatula R98 A180 A181 L367 F390 14 Fragaria vescasubsp. vesca R98 A177 G178 L368 F391 15 Citrus clementina R98 A180 A181L370 F393 16 Citrus clementina R98 A180 A181 L370 F393 17 Cicerarietinum R98 A180 A181 L367 F390 18 Cucumis sativus R98 A180 G181 L368F391 19 Cucumis sativus R93 A175 G176 L363 F386 20 Nicotiana tabacum R98G178 G179 L369 F392 21 Solanum lycopersicum R95 G175 G176 L366 F389 22Arabidopsis thaliana R101 A182 A183 L371 F394 23 Arabidopsis lyratasubsp. R103 A186 A187 L375 F398 lyrata 24 Arabidopsis thaliana R101 A182A183 L364 F387 25 Arabidopsis thaliana R147 A228 A229 L410 F433 26Ambrosia artemisiifolia R74 G151 G152 L336 F359 27 Setaria italica R128A213 G214 L408 F431 28 Sorghum bicolor R130 A215 G216 L410 F433 29Arabidopsis thaliana R101 A152 A153 L341 F364 30 Zea mays R130 A215 G216L410 F433 31 Zea mays R130 A215 G216 L410 F433 32 LEMPA R105 G188 G189L381 F404 33 LEMPA R150 A226 G227 L409 Y432 34 Populus trichocarpa R100A182 G183 L373 F396 35 Capsella rubella R165 A248 A249 L433 F456 36Brachypodium R134 A219 G220 L414 F437 distachyon 37 Oryza sativaJaponica R95 G179 G180 L374 F397 Group 38 Picea sitchensis R100 G186A187 L354 F377 39 Solanum tuberosum R98 G178 G179 L369 F392 40 Oryzasativa Indica R139 G224 G225 L419 F442 Group 41 Oryza sativa JaponicaR139 G224 G225 L419 F442 Group 42 Eutrema salsugineum R96 A179 A180 L368F391 43 Selaginella moellendorffii R97 G175 S176 L377 F400 44Selaginella moellendorffii R97 G175 S176 L377 F400 45 Amaranthustuberculatus R128 G210 G211 — — 46 Amaranthus tuberculatus R128 G210 — —— 47 Zea mays — A67 G68 L262 F285 48 Aegilops tauschii R30 A96 G97 L291F314 49 Genlisea aurea R89 G168 G169 — — 50 Amborella trichopoda — — —L161 F184 51 Rhodothermus marinus R87 A162 G163 L330 F353 52Salinibacter ruber R87 A161 G162 L330 F353 53 Salinibacter ruber M8 R87A161 G162 L330 F353 54 Zea mays — — — L69 F92 55 Rhodothermus marinusR87 A162 G163 L330 F353 56 Caldithrix abyssi R86 A160 G161 L329 F352 57Opitutus terrae PB90-1 R103 A178 G179 L345 M368 58 Verrucomicrobia R91A166 G167 L332 Y355 bacterium 59 Ignavibacterium album R88 A163 G164L332 F355 60 Coraliomargarita sp. R88 G163 A164 L331 Y354 CAG:312 61Salisaeta longa R88 A163 G164 L329 F352 62 Ambrosia artemisiifolia R98G175 G176 — — 63 Melioribacter roseus P3M-2 R88 A163 G164 L333 F356 64Halothiobacillus R97 A170 G171 L343 F366 neapolitanus c2 65 Chondruscrispus Y98 S176 G177 L352 Y376 66 Rubritalea marina R88 A163 G164 L339M362 67 Acidobacteria bacterium R88 A161 G162 L330 F353 68Coraliomargarita R88 A163 G164 L323 F346 akajimensis DSM 45221 69Oscillochloris trichoides R90 S164 G165 L340 L363 DG6 70 Opitutaceaebacterium R86 A161 G162 L352 L375 TAV1 71 Amborella trichopoda R87 A173A174 L230 — 72 Opitutaceae bacterium R105 A180 G181 L368 L391 TAV5 73Chloroflexus sp. Y-400-fl R91 A166 G167 L335 L358 74 Leptospirillum sp.Group II R92 A167 S168 L335 F358 ‘5-way CG’ 75 Leptospirillumferriphilum R92 A167 S168 L335 F358 ML-04 76 Verrucomicrobia R89 A165A166 L334 Y357 bacterium SCGC AAA300-O17 77 Chloroflexus aggregans R92A167 G168 L336 L359 DSM 9485 78 Desulfurobacterium R86 A161 G162 L333M356 thermolithotrophum 79 Desulfurobacterium sp. R90 A165 G166 L332M355 TCS-1 80 Arthrospira platensis C1 R93 A176 G177 L352 Y375 81Leptospirillum sp. Group II R92 A167 S168 L335 F358 ‘C75’ 82Verrucomicrobiae R87 A164 G165 L332 M355 bacterium DG1235 83Verrucomicrobia R89 A165 A166 L334 F357 bacterium SCGC AAA300-K03 84Synechococcus sp. JA-3-3Ab R101 A177 G178 L350 F373 85 Hymenobacternorwichensis R86 A161 G162 A321 F344 86 Pontibacter sp. BAB1700 R85 G159G160 S319 Y342 87 Leptospirillum R92 A172 S173 L339 F362ferrodiazotrophum 88 Prevotella histicola C89 A164 G165 L328 F351 F041189 Flexithrix dorotheae R84 A158 G159 A313 F336 90 Geobacter R93 A168G169 L342 M365 metallireducens GS-15 91 Synechococcus sp. JA-2- R93 A169G170 L362 F385 3B′a(2-13) 92 Crinalium epipsammum R85 A168 G169 L344F367 PCC 9333 93 Planctomyces mans A99 T187 S188 F358 F381 94 GeobacterR93 A170 G171 L344 M367 uraniireducens Rf4 95 Acidithiobacillus R87 A162G163 L323 F346 ferrivorans 96 Prevotella melaninogenica C88 A163 G164L327 F350 97 Thermovibrio ammonificans R86 A160 G161 L333 M356 98Brassica_rapa R143 A219 G220 L402 Y425 99 Brassica_rapa R112 A195 A196L384 F407 100 Gossypium R146 A222 G223 L405 Y428 101 Gossypium R98 A180G181 L370 F393 102 Conyza_canadensis R142 A218 G219 L401 Y424 103Conyza_canadensis R102 G179 G180 L365 F388 104 Kochia_scobaria R172 A248G249 L431 F454 105 Lolium_rigidum R138 A214 G215 L397 Y420 106Lolium_rigidum R97 A182 G183 L377 F400 107 Gossypium hirsutum PPO1 R146A222 G223 L405 Y428 108 Beta vulgaris PPO1 R167 A243 G244 L426 Y449 109Hordeum vulgare PPO1 R137 A213 G214 L396 Y419 110 Hordeum vulgare PPO2R142 A227 G228 L422 F445 111 Triticum aestivum PPO1 R138 A214 G215 L397Y420 112 Solanum lycopersicum PPO2 R95 G175 G176 L366 F389 113 Triticumaestivum PPO1_v2 R153 A229 G230 L412 Y435 114 Gossypium hirsutum PPO1_v2R146 A222 G223 L405 Y428 115 Gossypium hirsutum PPO2 R98 A180 G181 L370F393 116 Beta vulgaris PPO1_v2 R167 A243 G244 L426 Y449 117 Brassicanapus_PPO2 R99 A182 A183 L371 F394 637 Oryza sativa_PPO2 R139 G225 L419F442

TABLE 2a-2 Additional single amino acid substitutions within referenceto SEQ ID NO: 1, or 637 SEQ Mutated Mutated ID Organism site 6 site 7 1Amaranthus tuberculatus G398 L400 637 Oryza sativa_PPO2 G420 L422

In a further particularly preferred embodiment, the variant orderivative of the mutated PPO refers to SEQ ID NO: 1, 2, 3, 4, 5, 6, 7,8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25,26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43,44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61,62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79,80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97,98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112,113, 114, 115, 116, 117, or 637, comprising a single amino acidsubstitutions at the positions depicted in the following Table 2b.

It should be noted that Mutated site 1 of Table 2a) corresponds to Pos 1of Table 2b); Mutated site 2 of Table 2a) corresponds to Pos 16 of Table2b); Mutated site 3 of Table 2a) corresponds to Pos 17 of Table 2b);Mutated site 4 of Table 2a) corresponds to Pos 38 of Table 2b); Mutatedsite 5 of Table 2a) corresponds to Pos 42 of Table 2b).

TABLE 2b Pos Pos Pos Pos Pos Pos Pos Pos Pos Pos Pos Pos Pos Pos Pos PosPos Pos Pos ID 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 1 R128Y129 A131 S149 I151 A154 P164 K169 E182 S183 E189 F196 D202 C209 G210G211 L216 M218 H219 2 R128 Y129 A131 S149 I151 A154 P164 K169 E182 S183E189 F196 D202 C209 G210 G211 L216 M218 H219 3 R128 Y129 A131 S149 I151A154 P164 K169 E182 S183 E189 F196 D202 C209 G210 — L215 M217 H218 4R128 Y129 A131 S149 I151 A154 P164 K169 E182 S183 E189 F196 D202 C209G210 — L215 M217 Y218 5 R128 Y129 A131 S149 I151 A154 P164 K169 E182S183 E189 F196 D202 C209 G210 G211 L216 V218 H219 6 R98 Y99 A101 S119I121 A124 P134 K139 E152 S153 E159 F166 D172 C179 G180 G181 L186 M188H189 7 R127 Y128 A130 S148 I150 A153 P163 K168 E181 S182 E188 F195 D201S208 G209 G210 L215 M217 R218 8 R100 Y101 V103 S121 I123 A126 P136 K141E154 S155 Q161 V168 D174 S181 G182 G183 L188 M190 H191 9 R99 Y100 V102S120 I122 A125 P135 K140 E153 S154 Q160 V167 D173 S180 A181 G182 L187V189 C190 10 R98 Y99 V101 S119 I121 A124 P134 K139 E152 S153 Q159 V166D172 S179 A180 G181 L186 M188 R189 11 R98 Y99 V101 S119 L121 A124 P134R139 E152 S153 E159 V166 D172 S179 A180 A181 L186 M188 R189 12 R96 Y97V99 S117 F119 A122 P132 D137 E147 S148 Q154 V161 D167 S174 A175 G176L181 M183 R184 13 R98 Y99 V101 S119 L121 A124 P134 R139 E152 S153 E159V166 D172 S179 A180 A181 L186 I188 R189 14 R98 Y99 A101 S119 F121 T124P134 K139 E149 S150 Q156 V163 D169 S176 A177 G178 L183 M185 P186 15 R98Y99 V101 S119 F121 A124 P134 K139 E152 S153 Q159 V166 D172 S179 A180A181 L186 M188 R189 16 R98 Y99 V101 S119 F121 A124 P134 K139 E152 S153Q159 V166 D172 S179 A180 A181 L186 M188 R189 17 R98 Y99 V101 S119 L121A124 P134 R139 E152 S153 E159 V166 D172 S179 A180 A181 L186 M188 R189 18R98 Y99 V101 S119 F121 A124 P134 K139 E152 S153 Q159 V166 D172 S179 A180G181 L186 M188 S189 19 R93 Y94 V96 S114 F116 A119 P129 K134 E147 S148Q154 V161 D167 S174 A175 G176 L181 M183 S184 20 R98 Y99 A101 S119 F121T124 P134 N139 E150 S151 Q157 V164 D170 C177 G178 G179 L184 M186 H187 21R95 Y96 A98 S116 F118 T121 P131 N136 E147 S148 Q154 V161 D167 C174 G175G176 L181 M183 H184 22 R101 Y102 V104 S122 V124 T127 P137 K142 E154 S155Q161 V168 D174 S181 A182 A183 L188 M190 K191 23 R103 Y104 V106 S124 V126T129 P139 K144 E158 S159 Q165 V172 D178 S185 A186 A187 L192 M194 K195 24R101 Y102 V104 S122 V124 T127 P137 K142 E154 S155 Q161 V168 D174 S181A182 A183 L188 M190 K191 25 R147 Y148 V150 S168 V170 T173 P183 K188 E200S201 Q207 V214 D220 S227 A228 A229 L234 M236 K237 26 R74 Y75 V77 S95 F97T100 P110 K115 E123 S124 Q130 V137 D143 S150 G151 G152 L157 M159 R160 27R128 Y129 V131 S149 V151 T154 P164 K169 E185 S186 E192 V199 D205 S212A213 G214 L219 I221 R222 28 R130 Y131 V133 S151 V153 T156 P166 K171 E187S188 E194 V201 D207 S214 A215 G216 L221 I223 C224 29 R101 Y102 V104 — —— — — E124 S125 Q131 V138 D144 S151 A152 A153 L158 M160 K161 30 R130Y131 V133 S151 V153 T156 P166 K171 E187 S188 E194 V201 D207 S214 A215G216 L221 I223 R224 31 R130 Y131 V133 S151 V153 T156 P166 K171 E187 S188E194 V201 D207 S214 A215 G216 L221 I223 R224 32 R105 Y106 V108 S126 L128T131 P141 R146 E160 S161 Q167 V174 D180 S187 G188 G189 L194 M196 P197 33R150 F151 L153 F171 L173 I176 A186 P191 E201 E202 — V212 E218 Y225 A226G227 L232 M234 K235 34 R100 Y101 V103 S121 F123 A126 P136 K141 E154 S155Q161 V168 D174 S181 A182 G183 L188 A190 R191 35 R165 Y166 V168 S186 V188T191 P201 K206 E220 S221 R227 V234 D240 S247 A248 A249 L254 M277 K278 36R134 Y135 V137 S155 V157 T160 P170 K175 E191 S192 E198 V205 D211 S218A219 G220 L225 I227 R228 37 R95 Y96 V98 S116 V118 T121 P131 K136 E152S153 C158 V165 D171 S178 G179 G180 L185 I187 R188 38 R100 Y101 V103 S121T123 A126 P136 H141 E158 S159 R165 V172 D178 A185 G186 A187 L192 I194R195 39 R98 Y99 A101 S119 F121 T124 P134 N139 E150 S151 Q157 V164 D170C177 G178 G179 L184 M186 H187 40 R139 Y140 V142 S160 V162 T165 P175 K180E196 S197 C213 V220 D229 S233 G234 G235 L240 I242 R243 41 R139 Y140 V142S160 V162 T165 P175 K180 E196 S197 C213 V220 D229 S233 G234 G235 L240I242 R243 42 R96 Y97 V99 S117 V119 T122 P132 K137 E151 S152 Q158 V165D171 S178 A179 A180 L185 M187 K188 43 R97 Y98 V100 T118 L120 A123 P133R138 E147 S148 E154 I161 D167 S174 G175 S176 I181 I183 R184 44 R97 Y98V100 T118 L120 A123 P133 R138 E147 S148 E154 I161 D167 S174 G175 S176I181 I183 R184 45 R128 Y129 A131 S149 I151 A154 P164 K169 E182 S183 E189F196 D202 C209 G210 G211 L216 M218 H219 46 R128 Y129 A131 S149 I151 A154P164 K169 E182 S183 E189 F196 D202 C209 G210 — L215 M217 H218 47 — — —S3 V5 T8 P18 K23 E39 S40 E46 V53 D59 S66 A67 G68 L73 I75 R76 48 R30 Y31V33 — — — P47 K52 E68 S69 E75 V82 D88 S95 A96 G97 L102 I104 R105 49 R89Y90 V92 S110 I112 S115 P125 Q130 E140 S141 Q147 V154 D160 S167 G168 G169L174 M176 R177 50 — — — — — — — — — — — — — — — — — — — 51 R87 F88 V90T108 L110 P113 P123 H126 A137 K138 — V148 E154 F161 A162 G163 L168 V170R171 52 R87 Y88 V90 T108 L110 T113 P123 G126 A136 R137 — V147 A153 F160A161 G162 L167 V169 Q170 53 R87 Y88 V90 T108 L110 T113 P123 G126 A136R137 — V147 A153 F160 A161 G162 L167 V169 Q170 54 — — — — — — — — — — —— — — — — — — — 55 R87 F88 V90 T108 L110 P113 P123 H126 A137 K138 — V148E154 F161 A162 G163 L168 V170 R171 56 R86 Y87 V89 T107 L109 W112 P122P125 A135 D136 — F146 N152 Y159 A160 G161 L166 A168 P169 57 R103 Y104V106 S124 L126 P129 L139 R142 A153 E154 — F164 N170 Y177 A178 G179 L184A186 R187 58 R91 Y92 I94 T112 L114 L117 P127 A130 A141 A142 — F152 N158Y165 A166 G167 L172 V174 Q175 59 R88 Y89 L91 T109 L111 A114 P124 G127A138 E139 — F149 N155 Y162 A163 G164 L169 V171 K172 60 R88 F89 A91 T109L111 F114 P124 K127 A138 D139 — V149 N155 Y162 G163 A164 L169 I171 K17261 R88 F89 V91 T109 L111 T114 P124 A127 A138 S139 — V149 D155 F162 A163G164 L169 L171 K172 62 R98 Y99 V101 S119 F121 T124 P134 K139 E147 S148Q154 V161 D167 S174 G175 G176 — — — 63 R88 Y89 L91 T109 L111 S114 P124S127 A138 E139 — F149 D155 F162 A163 G164 L169 V171 K172 64 R97 F98 A100S118 L120 M123 A133 K136 A145 E146 — F156 D162 Y169 A170 G171 L176 V178Q179 65 Y98 Y99 M101 T119 L121 W124 P134 L139 S149 V150 Q155 V162 D168Y175 S176 G177 L182 M184 K185 66 R88 F89 I91 S109 I111 L114 P124 K127A138 D139 — P149 N155 Y162 A163 G164 L169 V171 E172 67 R88 Y89 V91 S109L111 W114 P124 G127 A136 D137 — F147 N153 Y160 A161 G162 L167 V169 R17068 R88 Y89 V91 T109 L111 I114 P124 K127 A138 D139 — L149 N155 Y162 A163G164 L169 L171 R172 69 R90 Y91 L93 M111 H113 M116 P126 P129 A139 S140 —V150 D156 Y163 S164 G165 M170 I172 K173 70 R86 F87 V89 T107 L109 L112L122 R125 G136 E137 — L147 D153 Y160 A161 G162 L167 A169 R170 71 R87 F88A90 S108 L110 P113 P123 S128 E145 S146 Q152 V159 D165 S172 A173 A174L179 — — 72 R105 F106 V108 T126 L128 L131 L141 R144 G155 E156 — L166D172 Y179 A180 G181 L186 A188 R189 73 R91 F92 L94 T112 L114 W117 P127N130 A141 A142 — A152 D158 Y165 A166 G167 L172 T174 A175 74 R92 Y93 V95T113 L115 W118 W128 P131 S142 H143 — A153 D159 Y166 A167 S168 L173 V175E176 75 R92 Y93 V95 T113 L115 W118 W128 P131 S142 H143 — A153 D159 Y166A167 S168 L173 V175 E176 76 R89 F90 I92 S110 F112 P115 P125 G128 A140E141 — V151 N157 Y164 A165 A166 L171 L173 K174 77 R92 Y93 L95 T113 L115W118 P128 N131 A142 A143 — A153 D159 Y166 A167 G168 L173 A175 A176 78R86 F87 Y89 S107 L109 W112 F122 P125 S136 E137 — A147 D153 F160 A161G162 L167 L169 K170 79 R90 F91 F93 S111 V113 F116 Y126 P129 S140 S141 —A151 D157 F164 A165 G166 L171 V173 K174 80 R93 Y94 Y96 S114 L116 A119A129 P134 T151 Q152 — V162 Q168 Y175 A176 G177 L182 V184 R185 81 R92 Y93V95 T113 L115 W118 W128 P131 S142 H143 — A153 D159 Y166 A167 S168 L173V175 E176 82 R87 Y88 V90 T108 L110 L113 P123 K126 A139 S140 — F150 D156Y163 A164 G165 L170 L172 E173 83 R89 F90 I92 S110 F112 P115 P125 G128A140 E141 — V151 N157 Y164 A165 A166 L171 L173 K174 84 R101 Y102 Y104S122 L124 V127 L137 P142 R152 Q153 — V163 E169 Y176 A177 G178 L183 A185V186 85 R86 Y87 L89 N107 F109 W112 L122 A126 D136 A137 — I147 N153 Y160A161 G162 L167 I169 H170 86 R85 Y86 L88 N106 L108 N111 R121 A126 S134D135 — Q145 A151 Y158 G159 G160 L165 V167 N168 87 R92 F93 L95 T113 I115L118 P128 P131 A147 D148 — F158 D164 Y171 A172 S173 L178 M180 A181 88C89 R90 I92 T111 L113 L116 P126 R129 G139 A140 — F150 D156 Y163 A164G165 L170 T172 R173 89 R84 Y85 F87 N105 F107 W110 L120 T125 A133 D134 —I144 N150 Y157 A158 G159 L164 M166 E167 90 R93 F94 Y96 S114 L116 W119P129 S132 A143 S144 — A154 S160 F167 A168 G169 M174 L176 R177 91 R93 Y94Y96 S114 L116 V119 L129 A134 R144 Q145 — V155 E161 Y168 A169 G170 L175A177 L178 92 R85 F86 Y88 S106 L108 L111 A121 P126 A143 Q144 — V154 A160Y167 A168 G169 L174 A176 R177 93 A99 L100 L102 T128 L130 P133 Y143 P146A162 Q163 — A173 Q179 Y186 T187 S188 L193 L195 R196 94 R93 F94 Y96 S114L116 W119 P129 A134 A145 A146 — A156 A162 F169 A170 G171 M176 L178 V17995 R87 Y88 L90 G107 L109 W112 P122 S125 A137 D138 — A148 D154 F161 A162G163 L168 V170 Q171 96 C88 R89 I91 T110 L112 L115 P125 K128 G138 S139 —F149 D155 Y162 A163 G164 L169 T171 R172 97 R86 F87 Y89 S107 L109 W112L122 P125 A135 E136 — A146 D152 F159 A160 G161 M166 L168 K169 98 R143F144 L146 F164 L166 I169 A179 P184 E191 S192 R198 V205 E211 Y218 A219G220 L225 M227 K228 99 R112 Y113 V115 S133 V135 T138 P148 K153 E167 S168Q174 V181 D187 S194 A195 A196 L201 M203 K204 100 R146 F147 L149 F167L169 I172 A182 P187 E194 S195 R201 V208 E214 Y221 A222 G223 L228 M230K231 101 R98 Y99 V101 S119 I121 A124 P134 K139 E152 S153 Q159 V166 D172S179 A180 G181 L186 M188 C189 102 R142 F143 L145 F163 L165 L168 A178P183 E190 S191 R197 V204 E210 Y217 A218 G219 L224 M226 K227 103 R102Y103 V105 S123 L125 T128 P138 K143 E151 S152 Q158 V165 N171 S178 G179G180 L185 M187 R188 104 R172 F173 L175 F193 L195 F198 A208 P213 E220S221 R227 V234 E240 Y247 A248 G249 L254 M256 K257 105 R138 F139 L141F159 L161 I164 A174 P179 E186 S187 R193 V200 E206 Y213 A214 G215 L220M222 R223 106 R97 Y98 V100 S118 L120 T123 P133 K138 E154 S155 E161 V168D174 S181 A182 G183 L188 I190 R191 107 R146 F147 L149 F167 L169 I172A182 P187 E194 S195 R201 V208 E214 Y221 A222 G223 L228 M230 K231 108R167 F168 L170 F188 L190 I193 A203 P208 E215 S216 R222 V229 E235 Y242A243 G244 L249 M251 K252 109 R137 F138 L140 F158 L160 V163 A173 P178E185 S186 R192 V199 E205 Y212 A213 G214 L219 M221 K222 110 R142 Y143V145 S163 V165 T168 P178 K183 E199 S200 E206 V213 D219 S226 A227 G228L233 I235 R236 111 R138 F139 L141 F159 L161 I164 A174 P179 E186 S187R193 V200 E206 Y213 A214 G215 L220 M222 K223 112 R95 Y96 A98 S116 F118T121 P131 N136 E147 S148 Q154 V161 D167 C174 G175 G176 L181 M183 H184113 R153 F154 L156 F174 L176 I179 A189 P194 E201 S202 R208 V215 E221Y228 A229 G230 L235 M237 K238 114 R146 F147 L149 F167 L169 I172 A182P187 E194 S195 R201 V208 E214 Y221 A222 G223 L228 M230 K231 115 R98 Y99M101 S119 I121 A124 P134 N139 E152 S153 Q159 V166 D172 S179 A180 G181L186 M188 C189 116 R167 F168 L170 F188 L190 I193 A203 P208 E215 S216R222 V229 E235 Y242 A243 G244 L249 M251 K252 117 R99 Y100 V102 S120 V122T125 P135 N141 E154 S155 Q161 V168 D174 S181 A182 A183 L188 M190 K191Pos Pos Pos Pos Pos Pos Pos Pos Pos Pos Pos Pos Pos Pos Pos Pos Pos PosPos ID 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 1 H220N227 S234 S246 K259 P260 R261 L295 Q301 G308 S324 R335 G346 F349 L351D352 T358 L384 L397 2 H220 N227 S234 S246 K259 P260 R261 L295 Q301 G308S324 R335 G346 F349 L351 D352 T358 L384 L397 3 H219 N226 S233 S245 K258P259 R260 L294 Q300 G307 S323 R334 G345 F348 L350 D351 T357 L383 L396 4H219 N226 S233 S245 K258 P259 R260 L294 Q300 G307 S323 R334 G345 F348L350 D351 T357 L383 L396 5 H220 N227 S234 S246 K260 P261 R262 L296 Q302G309 S325 R336 G347 F350 L352 D353 T359 L385 L398 6 H190 N197 S204 S216K230 P231 R232 L266 Q272 G279 S295 R306 G317 F320 L322 D323 S329 L355L368 7 H219 N226 S233 S245 K259 P260 R261 L295 H301 E308 P324 N335 E346F349 L351 D352 S358 L384 L397 8 H192 N199 S206 A218 K232 K234 R235 L269H275 E282 S300 C311 G322 F325 L327 D328 S334 L360 L373 9 H191 N198 S205T217 K231 K233 Q234 F268 P274 E281 S299 C310 R321 F324 L326 N327 S333L359 L372 10 H190 D197 S204 A216 K229 K231 P232 L266 H272 E279 S297 C308G319 F322 L324 N325 S331 L357 L370 11 H190 N197 S204 A216 K230 K232 H233L267 H273 Q280 D294 Y305 G316 F319 L321 N322 S328 L354 L367 12 H185 N192S199 A211 K225 K227 R228 L262 Q268 E275 S293 C304 G315 F318 L320 D321V327 L353 L366 13 H190 N197 S204 G216 K230 K232 H233 L267 H273 Q280 D294G305 G316 F319 L321 N322 T328 L354 L367 14 H187 N194 S201 S213 K227 K229R230 L264 H270 E277 S295 C306 G317 F320 L322 D323 N329 L355 L368 15 H190N197 S204 A216 K230 H232 R233 L267 H273 E280 S297 C308 G319 F322 L324D325 I331 L357 L370 16 H190 N197 S204 A216 K230 H232 R233 L267 H273 E280S297 C308 G319 F322 L324 D325 I331 L357 L370 17 H190 N197 S204 G216 K230K232 H233 L267 H273 E280 D294 G305 G316 F319 L321 N322 T328 L354 L367 18H190 N197 S204 T216 K230 K232 P233 L267 — Q279 I295 C306 G317 F320 L322N323 A329 L355 L368 19 H185 N192 S199 T211 K225 K227 P228 L262 — Q274I290 C301 G312 F315 L317 N318 A324 L350 L363 20 H188 N195 S202 P214 N228K230 R231 L265 C271 D278 S296 C307 G318 F321 L323 N324 D330 L356 L369 21L185 N192 S199 P211 N225 K227 R228 L262 C268 D275 S293 C304 G315 F318L320 N321 D327 L353 L366 22 H192 N199 S206 A218 T232 K234 G235 L269 —E280 H298 C309 G320 F323 L325 N326 N332 L358 L371 23 H196 N203 S210 A222T236 R238 G239 L273 — E284 H302 C313 G324 F327 L329 N330 N336 L362 L37524 H192 N199 S203 A215 T229 K231 G232 L266 — E277 H295 C302 G313 F316L318 N319 N325 L351 L364 25 H238 N245 S249 A261 T275 K277 G278 L312 —E323 H341 C348 G359 F362 L364 N365 N371 L397 L410 26 H161 D168 S175 S187N197 K199 R200 L234 C240 G246 S263 N274 G285 F288 L290 N291 S297 L323L336 27 H223 N230 S237 A249 K263 R265 N266 L300 F306 G313 T334 S345 G356F359 L361 D362 N368 L394 L408 28 H225 N232 S239 A251 K265 R267 N268 L302L308 G315 T336 S347 G358 F361 L363 D364 D370 L396 L410 29 H162 N169 S176A188 T202 K204 G205 L239 — E250 H268 C279 G290 F293 L295 N296 N302 L328L341 30 H225 N232 S239 A251 K265 R267 N268 L302 F308 G315 T336 S347 G358V361 L363 D364 D370 L396 L410 31 H225 N232 S239 A251 K265 R267 N268 L302F308 G315 T336 S347 G358 V361 L363 D364 D370 L396 L410 32 H198 N205 S212D224 K238 R240 — L274 H280 D287 F308 G319 G330 F333 L335 D336 T342 L368L381 33 A236 K243 S250 R262 P275 P277 K278 G312 N318 Y325 N335 Y346 —N357 A359 A360 Y367 L399 L409 34 H192 N199 S206 A218 K232 K234 R235 L269Y275 E282 S300 C311 R322 F325 L327 D328 S334 L360 L373 35 H279 N286 S293A305 — — — L331 — E342 H360 C371 G382 F385 L387 N388 K394 L420 L433 36H229 D236 S243 A255 K269 R271 N272 L306 C312 D319 L340 S351 G362 F365L367 D368 D374 L400 L414 37 H189 N196 S203 T215 K229 R231 N232 L266 C272G279 S300 S311 G322 F325 L327 D328 D334 L360 L374 38 H196 D203 S210 R222Q236 K237 R238 L272 L278 N285 S306 — — — — — T315 L341 L354 39 L188 N195S202 P214 N228 K230 R231 L265 C271 D278 S296 C307 G318 F321 L323 N324D330 L356 L369 40 H244 N251 S258 T270 K284 R286 N287 L321 C327 G334 S355S366 G377 F380 L382 D383 D389 L415 L429 41 H244 N251 S258 T270 K284 R286N287 L321 C327 G334 S355 S366 G377 F380 L382 D383 D389 L415 L429 42 H189N196 S203 A215 T229 K231 G232 L266 — E277 H295 C306 G317 F320 L322 N323K329 L355 L368 43 H185 S192 S199 K211 T233 P235 R236 T270 Q276 Q283 T303D314 G325 Y328 L330 D331 I337 L363 L377 44 H185 S192 S199 K211 T233 P235R236 T270 Q276 Q283 T303 D314 G325 Y328 L330 D331 I337 L363 L377 45 H220N227 — — — — — — — — — — — — — — — — — 46 H219 N226 — — — — — — — — — —— — — — — — — 47 H77 N84 S91 A103 K117 R119 N120 L154 F160 G167 T188S199 G210 V213 L215 D216 D222 L248 L262 48 H106 N113 S120 A132 K146 R148S149 L183 C189 D196 S217 S228 G239 F242 L244 D245 D251 L277 L291 49 H178N185 S192 A204 N218 R220 R221 L255 N261 D268 G287 S298 — — — — — — — 50— — — S3 K17 K19 H20 L54 D60 S67 S88 R99 G110 Y113 L115 D116 M122 L148L161 51 Y172 E179 S186 — — A203 P204 L238 — P247 F262 H273 P282 D285 —R286 E293 L319 L330 52 H171 A178 S185 — — D204 T205 H238 — W247 S262H273 T282 D285 — L286 T293 L319 L330 53 H171 A178 S185 — — D204 T205H238 — W247 S262 H273 T282 D285 — L286 T293 L319 L330 54 — — — — — — — —— — — S6 G17 V20 L22 D23 D29 L55 L69 55 Y172 E179 S186 — — A203 P204L238 — P247 F262 H273 P282 D285 — R286 E293 L319 L330 56 A170 N177 S184R196 — K204 D205 R238 — — F261 Y272 S280 K283 R285 A286 L293 L319 L32957 Q188 E195 S202 R214 — E219 P220 D254 — K261 S276 P287 T296 E299 P301L302 E309 L335 L345 58 H176 A183 S190 R202 — K210 D211 E244 — — S263H274 D283 D286 D288 M289 I296 L322 L332 59 S173 A180 G187 R199 — K207Q208 I241 — — V264 Y275 K283 K286 F288 K289 Y296 L322 L332 60 H173 N180S187 — G203 F205 F206 I239 S243 — — P273 M283 A286 L288 A289 Q295 L321L331 61 H173 E180 S187 G199 — A207 T208 T241 — T250 — H272 P281 D284 —T285 P292 L318 L329 62 — — — — — — — — — — — — — — — — — — — 63 S173R180 G187 R199 — K207 Q208 L241 — Q250 T265 Y276 E284 Q287 L289 A290Y297 L323 L333 64 A180 A187 S194 A206 — — A217 D250 I256 G263 H275 H286— G297 L299 A300 E307 L333 L343 65 H186 R193 S200 T212 T222 K224 E225T259 T265 G272 — H292 A303 K306 F308 K309 K316 L342 L352 66 H173 Q180S187 Q199 H207 L209 Q210 G244 R250 — S270 H281 E290 L293 S295 L296 D303L329 L339 67 F171 A178 G185 R197 — K205 I206 L239 — — R262 Y273 R281P284 A286 A287 V294 L320 L330 68 Y173 A180 G187 — G204 K206 A207 E240Q244 — — H270 — E278 P280 I281 D287 L313 L323 69 A174 E181 S188 K200G212 K214 M215 T249 — G257 E272 Y283 — P294 A296 A297 R304 L330 L340 70Y171 E178 S185 R197 P209 P211 P212 V246 V252 A257 R283 E294 A303 E306P308 L309 E316 L342 L352 71 — — — — — — — T184 C190 L197 — S213 — — — —— — L230 72 Y190 E197 S204 R216 P228 P230 P231 V265 V271 A276 R299 E310A319 E322 P324 L325 E332 L358 L368 73 A176 E183 S190 K202 — K209 M210V244 — W252 I267 F278 — Q289 A291 A292 P299 L325 L335 74 A177 R184 G191R203 G209 S211 P212 V243 — G252 T267 P278 — D289 P291 S292 P299 L325L335 75 A177 R184 G191 R203 G209 S211 P212 V243 — G252 T267 P278 — D289P291 S292 P299 L325 L335 76 Y175 D182 S189 — E203 I205 S206 K239 K244 —V264 H275 I285 S288 L290 L291 Y298 L324 L334 77 A177 E184 S191 K203 —K210 M211 V245 — Y253 T268 Y279 — P290 A292 A293 P300 L326 L336 78 A171Y178 G185 A197 P206 G208 P209 I241 — G250 T265 Y276 — L287 L289 S290E297 L323 L333 79 A175 H182 G189 K201 T205 G207 P208 V240 — K249 S264Y275 — E286 L288 A289 E296 L322 L332 80 S186 A193 G200 K212 P224 T226R227 R261 H267 F274 E284 H295 — S306 I308 A309 P316 L342 L352 81 A177R184 G191 R203 G209 A211 P212 V243 — G252 T267 P278 — E289 P291 S292P299 L325 L335 82 H174 G181 S188 — G204 A206 Y207 V240 R244 — F263 H274E283 A286 P288 L289 E296 L322 L332 83 Y175 D182 S189 — E203 I205 S206K239 K244 — V264 H275 I285 S288 L290 L291 Y298 L324 L334 84 A187 G194S201 — P223 P225 K226 Q260 G265 F272 A282 Y293 — P304 A306 S307 L314L340 L350 85 K171 A178 S185 A197 — — G198 L232 G238 S245 S253 F264 —P275 A277 A278 H285 L311 A321 86 K169 E176 S183 G195 — — V196 F229 G235A242 E251 H262 — P273 M275 S276 N283 L309 S319 87 D182 Q189 S196 Q207P213 F215 A216 V247 — G256 R271 A282 — P293 I295 P296 P303 L329 L339 88L174 N181 S188 P200 — R207 A208 L242 G248 K250 I261 Y272 — K283 Q285L286 Y293 L318 L328 89 K168 E175 S182 T194 — — Q195 E227 G233 — K245Y256 — P267 S269 A270 N277 L303 A313 90 S178 E185 S192 K204 A217 G219P220 V253 — — D274 H285 — A296 M298 A299 P306 L332 L342 91 A179 G186S193 R205 P226 P228 K229 H263 E268 F275 A294 Y305 — P316 A318 S319 P326L352 L362 92 S178 Q185 G192 R204 P216 V218 R219 E253 N259 F266 E276 Y287— P298 A300 S301 P308 L334 L344 93 A197 D204 S211 T223 T229 A231 R232V266 — G275 H290 P301 — P312 L314 S315 E322 V348 F358 94 S180 E187 G194K206 A219 G221 P222 V255 — — D276 Y287 — G298 M300 S301 P308 L334 L34495 A172 A179 S186 A194 — — — E236 — S244 Q255 G266 — A277 L279 A280 P287L313 L323 96 L173 D180 S187 P199 — R206 A207 L241 G247 K249 I260 Y271 —K282 Q284 L285 Y292 L317 L327 97 A170 R177 G184 A196 P206 G208 P209 V241— K250 E265 Y276 — R287 L289 S290 E297 L323 L333 98 A229 K236 S243 A254K269 P270 K271 S304 — G312 — — L348 S351 A353 E354 Y360 L386 L402 99H205 N212 S219 A231 K246 K247 G248 L282 T288 E293 H311 C322 G333 F336L338 N339 K345 L371 L384 100 A232 K239 S246 E257 K272 P273 K274 S307 —G315 — — L351 A354 A356 D357 Y363 L389 L405 101 H190 D197 S204 A216 R230K231 A232 L266 H272 E279 S297 C308 G319 F322 L324 N325 S331 L357 L370102 A228 K235 S242 A253 T268 P269 K270 V303 — R311 — — L347 E350 A352D353 Y359 L385 L401 103 Y189 D196 S203 S215 S226 K227 R228 L262 C268G274 P292 G303 G314 F317 L319 N320 S326 L352 L365 104 A258 V265 N272E283 K298 P299 K300 A333 — G341 — — F377 A380 A382 D383 H389 L415 L431105 A224 R231 S238 D249 T264 P265 K266 T299 — Q307 — — L343 D346 A348D349 Y355 L381 L397 106 H192 N199 S206 A218 G233 R234 N235 L269 C275N282 P303 S314 G325 F328 L330 D331 D337 L363 L377 107 A232 K239 S246R258 K272 P273 K274 S307 G313 T320 S334 S345 A356 L359 Q361 F362 A368L395 L405 108 A253 K260 S267 R279 K293 P294 K295 S328 L334 T341 S355S366 A377 L380 K382 F383 A389 L416 L426 109 A223 R230 S237 K249 A263P264 K265 T298 D304 G311 S325 S336 A347 L350 K352 F353 A359 L386 L396110 H237 N244 S251 A263 G278 R279 N280 L314 C320 D327 S348 S359 G370F373 L375 D376 D382 L408 L422 111 A224 R231 S238 K250 A264 P265 K266T299 D305 G312 S326 S337 A348 L351 K353 F354 A360 L387 L397 112 L185N192 S199 P211 K226 K227 R228 L262 C268 D275 S293 C304 G315 F318 L320N321 D327 L353 L366 113 A239 R246 S253 K265 A279 P280 K281 T314 D320G327 S341 S352 A363 L366 K368 F369 A375 L402 L412 114 A232 K239 S246R258 K272 P273 K274 S307 G313 T320 S334 S345 A356 L359 Q361 F362 A368L395 L405 115 H190 D197 S204 A216 R230 K231 A232 L266 H272 E279 S297C308 G319 F322 L324 N325 S331 L357 L370 116 A253 K260 S267 R279 K293P294 K295 S328 L334 T341 S355 S366 A377 L380 K382 F383 A389 L416 L426117 H192 N199 S206 A218 K233 K234 G235 L269 A275 E280 H298 C309 G320F323 L325 N326 K332 L358 L371 Pos Pos Pos Pos Pos Pos Pos Pos Pos PosPos Pos Pos Pos Pos Pos Pos Pos ID 39 40 41 42 43 44 45 46 47 48 49 5051 52 53 54 55 56 1 F417 T418 T419 F420 A432 T434 K438 L449 T451 F462Y470 S476 V477 D482 Y493 K498 E515 K528 2 F417 T418 T419 F420 A432 T434K438 L449 T451 F462 Y470 S476 V477 D482 Y493 K498 E515 K528 3 F416 T417T418 F419 A431 T433 K437 L448 T450 F461 Y469 C475 V476 D481 Y492 K497E514 K527 4 F416 T417 T418 F419 A431 T433 K437 L448 T450 F461 Y469 S475V476 D481 Y492 K497 E514 K527 5 F418 T419 T420 F421 A433 T435 K439 L450T452 F463 Y471 S477 V478 D483 Y494 K499 E516 K529 6 F388 T389 T390 F391A403 T405 K409 L420 T422 F433 Y441 S447 V448 D453 Y464 K469 E486 K499 7Y417 T418 T419 F420 A432 T434 K438 L449 T451 Y462 Y470 S476 V477 E482Y493 K498 E515 K525 8 Y393 T394 T395 F396 A408 T410 K414 L425 A427 Y438F446 S452 V453 D458 Y469 K474 D491 K504 9 Y392 T393 T394 F395 A407 T409K413 L424 A426 Y437 Y445 A451 V452 D457 Y468 K473 D490 K503 10 Y390 T391T392 F393 A405 T407 K411 L422 V424 Y435 Y443 S449 V450 E455 Y466 K471D488 K500 11 Y387 T388 T389 F390 A402 T404 R408 L419 A421 Y432 Y440 S446V447 D452 F463 K468 D485 T498 12 Y386 T387 T388 F389 A401 T403 K407 L418A420 Y431 Y439 S445 V446 E451 Y462 R467 E484 K497 13 Y387 T388 T389 F390A402 T404 T408 L419 A421 F432 Y440 S446 V447 D452 Y463 R468 D485 S498 14Y388 T389 T390 F391 A403 K405 K409 L420 A422 Y433 Y441 S447 V448 E453Y464 R469 D486 K499 15 Y390 T391 T392 F393 A405 T407 K411 L422 V424 F435Y443 S449 V450 E455 Y466 K471 E488 K501 16 Y390 T391 T392 F393 A405 T407K411 L422 V424 F435 Y443 S449 V450 E455 Y466 K471 E488 K501 17 Y387 T388T389 F390 A402 T404 K408 L419 A421 Y432 Y440 L446 V447 D452 Y463 R468D485 T498 18 Y388 T389 T390 F391 S403 T405 K409 L420 V422 Y433 Y441 S447V448 E453 Y464 R469 D486 S499 19 Y383 T384 T385 F386 S398 T400 K404 L415V417 Y428 Y436 S442 V443 E448 Y459 R464 D481 S494 20 Y389 T390 T391 F392A404 R406 K410 L421 A423 Y434 Y442 S448 V449 D454 Y465 R470 D487 S500 21Y386 T387 T388 F389 A401 R403 K407 L418 A420 C431 Y439 S445 V446 D451Y462 K467 D484 T497 22 Y391 T392 T393 F394 A406 T408 K412 L423 V425 Y436Y444 S450 V451 D456 Y467 R472 D489 K502 23 Y395 T396 T397 F398 A410 T412K416 L427 V429 Y440 Y448 S454 V455 D460 Y471 R476 D493 K506 24 Y384 T385T386 F387 A399 T401 K405 L416 V418 Y429 Y437 S443 V444 D449 Y460 R465D482 K495 25 Y430 T431 T432 F433 A445 T447 K451 L462 V464 Y475 Y483 S489V490 D495 Y506 R511 D528 K541 26 Y356 T357 T358 F359 A371 R373 K377 L388T390 Y401 Y409 S415 V416 E421 Y432 K437 E454 K467 27 Y428 T429 T430 F431A443 T445 K449 L460 V462 Y473 Y481 S487 V488 E493 Y504 K509 E526 N539 28Y430 T431 T432 F433 A445 T447 K451 L462 V464 Y475 Y483 S489 V490 E495Y506 K511 D528 N541 29 Y361 T362 T363 F364 A376 T378 K382 L393 V395 Y406Y414 S420 V421 D426 Y437 R442 D459 K472 30 Y430 T431 T432 F433 A445 T447K451 L462 V464 Y475 Y483 S489 V490 E495 Y506 K511 D528 N541 31 Y430 T431T432 F433 A445 T447 K451 L462 V464 Y475 Y483 S489 V490 E495 Y506 K511D528 N541 32 Y401 T402 T403 F404 A416 L418 K422 L433 V435 Y446 Y454 L460V461 D466 Y477 R482 D499 — 33 L429 L430 N431 Y432 K444 E446 V450 L461K463 V476 F484 D490 L491 T496 L509 V514 A531 F544 34 Y393 T394 T395 F396— — — L402 C404 Y408 Y416 L422 V423 E428 Y439 R444 D461 K474 35 Y453T454 T455 F456 A468 T470 K474 L485 V487 Y498 Y506 S512 V513 D518 Y529R534 D551 K564 36 F434 T435 T436 F437 A449 T451 K455 L466 V468 H479 Y487L493 A494 G499 Y510 K515 D532 A543 37 Y394 T395 S396 F397 A409 T411 K415L426 V428 H439 Y447 L453 V454 A459 Y470 K475 D492 D505 38 F374 T375 T376F377 S389 L391 Q395 L406 V408 Y419 Y427 S433 V434 D439 F450 R455 D472T485 39 Y389 T390 T391 F392 A404 — — — — — — — — — — — — — 40 Y449 T450S451 F452 A464 T466 K470 L481 V483 H494 Y502 L508 V509 A514 Y525 — K537— 41 Y449 T450 S451 F452 A464 T466 K470 L481 V483 H494 Y502 L508 V509A514 Y525 — K537 — 42 Y388 T389 T390 F391 A403 T405 — — — — — — — — — —— — 43 F397 T398 T399 F400 R412 K414 L418 I429 V431 Y442 Y450 N456 V457Q462 Y473 R478 E495 K508 44 F397 T398 T399 F400 R412 K414 L418 I429 V431Y442 Y450 N456 V457 Q462 Y473 R478 E495 K508 45 — — — — — — — — — — — —— — — — — — 46 — — — — — — — — — — — — — — — — — — 47 Y282 T283 T284F285 A297 T299 K303 L314 V316 Y327 Y335 S341 V342 E347 Y358 K363 D380N393 48 F311 T312 T313 F314 A326 T328 K332 L343 V345 H356 Y364 S370 A371G376 — K383 D400 V413 49 — — — — — — — — — — — — — — — — — — 50 Y181T182 T183 F184 A196 L198 R202 L213 V215 Y226 Y234 M240 V241 E246 Y257S262 — — 51 L350 T351 T352 F353 L365 E367 E371 L382 I384 R395 Y403 A409V410 H415 L426 M431 R448 G461 52 L350 T351 T352 F353 S365 A367 Q371 L382V384 H395 Y403 T409 V410 D415 F426 R431 — A458 53 L350 T351 T352 F353S365 A367 Q371 L382 V384 H395 Y403 T409 V410 D415 F426 R431 — T458 54Y89 T90 T91 F92 A104 T106 K110 L121 V123 Y134 Y142 S148 V149 E154 Y165K170 D187 N200 55 L350 T351 T352 F353 L365 E367 E371 L382 I384 R395 Y403A409 V410 H415 L426 M431 R448 G461 56 F349 T350 T351 F352 K364 D366 K370V381 L383 R394 Y402 K408 I409 D414 F425 R430 E447 — 57 L365 T366 V367M368 L380 A382 L386 L397 V399 F410 Y418 H424 F425 A430 M441 R446 E463 —58 L352 S353 T354 Y355 L367 D369 D373 L384 V386 V397 Y405 K411 I412 N417F428 R433 Q450 — 59 F352 T353 L354 F355 E367 R369 L373 M384 I386 F397Y405 E411 H412 D417 I428 R433 N450 — 60 L351 T352 N353 Y354 L366 R368R372 L383 V385 V396 Y404 E410 Y411 D416 L427 R432 A449 — 61 L349 T350T351 F352 A364 D366 R370 L381 V383 A394 Y402 A408 A409 E414 F425 R430R447 V460 62 — — — — — — — — — — — — — — — — — — 63 F353 T354 L355 F356M368 K370 I374 M385 I387 L398 Y406 E412 H413 E418 L429 R434 K451 — 64L363 S364 A365 F366 G378 D380 L384 L395 I397 R408 Y416 E422 L423 S428L439 R444 E461 — 65 L373 T374 V375 Y376 R388 A390 V394 L405 V407 T418Y426 E432 S433 A438 F449 R454 E471 — 66 I359 N360 V361 M362 L374 E376R380 L391 V393 H404 L412 I418 V419 I424 L435 R440 E457 — 67 L350 T351T352 F353 R365 N367 I371 L382 L384 R395 Y403 E409 I410 D415 F426 R431E448 — 68 L343 T344 V345 F346 P358 T360 L364 L375 I377 H388 Y396 K402V403 T408 L419 R424 N441 — 69 T360 I361 N362 L363 Q375 D377 I381 I392A394 R405 Y413 E419 A420 E425 F436 R441 E458 A471 70 L372 T373 V374 L375M387 L389 M393 L404 V406 V417 Y425 R431 F432 E437 V448 R453 R470 — 71 —— — — — — — — — — — — — — — — — — 72 L388 T389 V390 L391 M403 L405 M409L420 V422 V433 Y441 R447 F448 E453 V464 R469 R486 — 73 T355 T356 T357L358 R370 D372 I376 L387 I389 R400 Y408 E414 R415 V420 F431 R436 E453A466 74 L355 T356 V357 F358 A370 D372 E376 L387 V389 R400 L408 E414 T415R420 L429 L434 E451 — 75 L355 T356 V357 F358 A370 D372 E376 L387 V389R400 L408 E414 T415 R420 L429 L434 E451 — 76 L354 T355 T356 Y357 L369Q371 L375 L386 I388 L399 P407 D413 R414 S419 I430 I435 — — 77 T356 I357T358 L359 Q371 E373 I377 L388 I390 R401 Y409 E415 R416 E421 L432 R437E454 A467 78 I353 R354 V355 M356 L368 D370 V374 M385 I387 K398 Y406 E412R413 F418 L429 Y434 R451 — 79 I352 R353 A354 M355 A367 E369 A373 M384I386 K397 Y405 E411 K412 F417 L428 Y433 E450 — 80 L372 S373 N374 Y375M387 D389 V393 L404 A406 L418 Y426 N432 R433 D438 L449 I454 S471 N484 81L355 T356 V357 F358 T370 D372 E376 L387 V389 R400 F408 E414 T415 R420L429 L434 E451 — 82 L352 T353 V354 M355 L367 Q369 L373 L384 L386 S397Y405 P411 W412 K417 F428 V433 E450 — 83 L354 T355 T356 F357 L369 Q371L375 L386 I388 L399 P407 D413 R414 S419 I430 I435 — — 84 F370 L371 S372F373 L394 P396 A400 L411 T413 L425 Y433 Q439 R440 Q445 V457 L462 Q479 —85 F341 T342 T343 F344 Q356 E358 K362 — D374 L387 Y395 — R398 H403 S416R421 D438 — 86 I339 T340 S341 Y342 L354 E356 L360 — Q372 L385 F393 —Y396 H401 I414 Y419 A436 — 87 L359 T360 V361 F362 A374 D376 L380 L391V393 R404 S412 E418 R419 E424 L433 L438 E455 — 88 Y348 A349 F350 F351K363 D365 R369 L380 Y382 R395 Y403 S409 R410 D415 I426 K431 E448 — 89I333 T334 S335 F336 L348 D350 K354 — K366 R378 Y386 — D389 H394 V407E412 E429 — 90 L362 R363 S364 M365 L377 D379 M383 M394 I396 R407 Y415K421 R422 Q427 L438 Y443 D460 — 91 L382 I383 S384 F385 L406 P408 A412L423 T425 L437 Y445 Q451 R452 Q457 V469 L474 Q491 — 92 L364 T365 N366F367 L379 N381 V385 L396 K398 L410 Y418 L424 R425 N430 L441 T446 P463 —93 L378 R379 T380 F381 H393 D395 N399 L410 V412 R423 Y431 Q437 L438 E443L454 Y459 E476 — 94 L364 R365 S366 M367 L379 D381 V385 M396 I398 R409Y417 R423 R424 E429 L440 Y445 D462 — 95 L343 T344 A345 F346 R357 D359L363 L374 I376 T387 Y395 D401 R402 D407 F418 R423 Q440 — 96 Y347 A348C349 F350 K362 D364 I368 L379 Y381 R394 Y402 A408 R409 D414 I425 K430E447 — 97 I353 R354 V355 M356 K368 E370 T374 M385 I387 R398 Y406 E412K413 F418 F429 Y434 E451 — 98 L422 L423 N424 Y425 K437 E439 V443 L454S458 V469 F477 D483 L484 K489 L502 V507 T524 — 99 Y404 T405 T406 F407A419 T421 K425 L436 I438 Y449 Y457 S463 V464 D469 Y480 R485 D502 N515100 L425 L426 N427 Y428 K440 E442 V446 L457 N461 V472 F480 D486 L487K492 L505 V510 A527 — 101 Y390 T391 T392 F393 A405 T407 K411 L422 V424Y435 Y443 S449 V450 E455 Y466 K471 D488 K500 102 L421 L422 N423 Y424K436 E438 V442 L453 K457 V468 F476 D482 I483 K488 L501 V506 A523 — 103Y385 T386 T387 F388 A400 R402 K406 L417 A419 Y430 Y438 L444 V445 E450Y461 K466 E483 K496 104 I451 L452 S453 F454 K466 Q468 A472 L483 S487V498 F506 D512 L513 K518 L531 V536 A553 — 105 L417 L418 N419 Y420 K432E434 V438 L449 T453 V464 F472 D478 R479 K484 L497 V502 S519 — 106 F397T398 T399 F400 A412 T414 K418 L429 V431 H442 Y450 S456 A457 G462 Y473K478 D495 D508 107 L425 L426 N427 Y428 K440 E442 V446 L457 N461 V472F480 D486 L487 K492 L505 V510 A527 — 108 I446 L447 S448 Y449 K461 K463A467 L478 D482 V493 F501 D507 L508 K513 L526 V531 A548 — 109 L416 L417N418 Y419 K431 E433 V437 L448 R452 V463 F471 D477 R478 K483 L496 V501S518 — 110 F442 T443 T444 F445 A457 T459 K463 L474 V476 H487 Y495 L501A502 G507 Y518 K523 D540 G549 111 L417 L418 N419 Y420 K432 E434 V438L449 R453 V464 F472 D478 R479 K484 L497 V502 S519 — 112 Y386 T387 T388F389 A401 R403 K407 L418 A420 C431 Y439 S445 V446 D451 Y462 K467 D484S494 113 L432 L433 N434 Y435 K447 E449 V453 L464 R468 V479 F487 D493R494 K499 L512 V517 S534 — 114 L425 L426 N427 Y428 K440 E442 V446 L457N461 V472 F480 D486 L487 K492 L505 V510 A527 — 115 Y390 T391 T392 F393A405 T407 K411 L422 V424 Y435 Y443 S449 V450 E455 Y466 K471 D488 S497116 I446 L447 S448 Y449 K461 K463 A467 L478 D482 V493 F501 D507 L508K513 L526 V531 A548 — 117 Y391 T392 T393 F394 A406 T408 K412 L423 V425Y436 Y444 S450 V451 D456 Y467 R472 D489 K502

Assays to test for the functionality of such mutants are readilyavailable in the art, and respectively, described in the Example sectionof the present invention.

In a preferred embodiment, the mutated PPO refers to a polypeptide ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, or 117, in whichthe amino acid sequence differs at Mutated site 1 (which corresponds toArg128 of SEQ ID NO: 1) according to Table 2a, and/or at Mutated site 5(which corresponds to Phe420 of SEQ ID NO: 1) according to Table 2a.

Examples of differences at these amino acid positions include, but arenot limited to, one or more of the following:

the amino acid at Mutated site 1 is other than Arginine (or Tryosine, orCysteine; as the case may be according to Table 2a);

the amino acid at Mutated site 5 is other than Phenylalanine (orMethionine, or Tyrosine, or Leucine, as the case may be according toTable 2a),

In particularly preferred embodiment, the mutated PPO comprises asequence of SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32,33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50,51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68,69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86,87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103,104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117,577, 579, 581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603,605, 607, 609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, avariant, derivative, orthologue, paralogue or homologue thereof, inwhich:

the amino acid at Mutated site 1 (which corresponds to Arg128 of SEQ IDNO: 1) is Leu, Ala, Val, Ile, Met, Tyr, Gly, Asn, Cys, Phe, Ser, Thr,Gln, or His, and the amino acid at Mutated site 5 (which corresponds toPhe420 of SEQ ID NO: 1) is Ala, Leu, Val, le, or Met.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Leu, and the amino acid at Mutatedsite 5 is Ala.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Leu, and the amino acid at Mutatedsite 5 is Leu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Leu, and the amino acid at Mutatedsite 5 is Val.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Leu, and the amino acid at Mutatedsite 5 is Ile.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Leu, and the amino acid at Mutatedsite 5 is Met.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Ala, and the amino acid at Mutatedsite 5 is Ala.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Ala, and the amino acid at Mutatedsite 5 is Leu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Ala, and the amino acid at Mutatedsite 5 is Val.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Ala, and the amino acid at Mutatedsite 5 is Ile.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Ala, and the amino acid at Mutatedsite 5 is Met.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Val, and the amino acid at Mutatedsite 5 is Ala.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Val, and the amino acid at Mutatedsite 5 is Leu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Val, and the amino acid at Mutatedsite 5 is Val.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Val, and the amino acid at Mutatedsite 5 is Ile.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Val, and the amino acid at Mutatedsite 5 is Met.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Ile, and the amino acid at Mutatedsite 5 is Ala.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Ile, and the amino acid at Mutatedsite 5 is Leu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Ile, and the amino acid at Mutatedsite 5 is Val.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Ile, and the amino acid at Mutatedsite 5 is Ile.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Ile, and the amino acid at Mutatedsite 5 is Met.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Met, and the amino acid at Mutatedsite 5 is Ala.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Met, and the amino acid at Mutatedsite 5 is Leu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Met, and the amino acid at Mutatedsite 5 is Val.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Met, and the amino acid at Mutatedsite 5 is Ile.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Met, and the amino acid at Mutatedsite 5 is Met.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Tyr, and the amino acid at Mutatedsite 5 is Ala.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Tyr, and the amino acid at Mutatedsite 5 is Leu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 76, 77,78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95,96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110,111, 112, 113, 114, 115, 116, 117, 577, 579, 581, 583, 585, 587, 589,591, 593, 595, 597, 599, 601, 603, 605, 607, 609, 611, 613, 615, 617,619, 621, 623, 625, 627, or 637, a variant, derivative, orthologue,paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Tyr, and the amino acid at Mutatedsite 5 is Val.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Tyr, and the amino acid at Mutatedsite 5 is Ile.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Tyr, and the amino acid at Mutatedsite 5 is Met.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Gly, and the amino acid at Mutatedsite 5 is Ala.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Gly, and the amino acid at Mutatedsite 5 is Leu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Gly, and the amino acid at Mutatedsite 5 is Val.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Gly, and the amino acid at Mutatedsite 5 is Ile.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Gly, and the amino acid at Mutatedsite 5 is Met.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Asn, and the amino acid at Mutatedsite 5 is Ala.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Asn, and the amino acid at Mutatedsite 5 is Leu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Asn, and the amino acid at Mutatedsite 5 is Val.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Asn, and the amino acid at Mutatedsite 5 is Ile.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Asn, and the amino acid at Mutatedsite 5 is Met.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Cys, and the amino acid at Mutatedsite 5 is Ala.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Cys, and the amino acid at Mutatedsite 5 is Leu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Cys, and the amino acid at Mutatedsite 5 is Val.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Cys, and the amino acid at Mutatedsite 5 is Ile.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Cys, and the amino acid at Mutatedsite 5 is Met.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Phe, and the amino acid at Mutatedsite 5 is Ala.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which: theamino acid at Mutated site 1 is Phe, and the amino acid at Mutated site5 is Leu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Phe, and the amino acid at Mutatedsite 5 is Val.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Phe, and the amino acid at Mutatedsite 5 is Ile.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Phe, and the amino acid at Mutatedsite 5 is Met.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Ser, and the amino acid at Mutatedsite 5 is Ala.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Ser, and the amino acid at Mutatedsite 5 is Leu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Ser, and the amino acid at Mutatedsite 5 is Val.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Ser, and the amino acid at Mutatedsite 5 is Ile.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Ser, and the amino acid at Mutatedsite 5 is Met.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Thr, and the amino acid at Mutatedsite 5 is Ala.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Thr, and the amino acid at Mutatedsite 5 is Leu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Thr, and the amino acid at Mutatedsite 5 is Val.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Thr, and the amino acid at Mutatedsite 5 is Ile.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Thr, and the amino acid at Mutatedsite 5 is Met.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Gln, and the amino acid at Mutatedsite 5 is Ala.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Gln, and the amino acid at Mutatedsite 5 is Leu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Gln, and the amino acid at Mutatedsite 5 is Val.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Gln, and the amino acid at Mutatedsite 5 is Ile.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is Gln, and the amino acid at Mutatedsite 5 is Met.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is His, and the amino acid at Mutatedsite 5 is Ala.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is His, and the amino acid at Mutatedsite 5 is Leu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is His, and the amino acid at Mutatedsite 5 is Val.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is His, and the amino acid at Mutatedsite 5 is Ile.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 1 is His, and the amino acid at Mutatedsite 5 is Met.

In another preferred embodiment, the mutated PPO refers to a polypeptideof SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116,or 117, in whichthe amino acid sequence differs at Mutated site 4 (which corresponds toLeu397 of SEQ ID NO: 1) according to Table 2a, and/or at Mutated site 5(which corresponds to Phe420 of SEQ ID NO: 1) according to Table 2a.

Examples of differences at these amino acid positions include, but arenot limited to, one or more of the following:

the amino acid at Mutated site 4 is other than Leucine (or Alanine, orSerine, or Phenylalanine, as the case may be according to Table 2a);

the amino acid at Mutated site 5 is other than Phenylalanine (orMethionine, or Tyrosine, or Leucine, as the case may be according toTable 2a),

In particularly preferred embodiment, the mutated PPO comprises asequence of SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32,33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50,51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68,69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86,87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103,104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117,577, 579, 581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603,605, 607, 609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, avariant, derivative, orthologue, paralogue or homologue thereof, inwhich:

the amino acid at Mutated site 4 (which corresponds to Leu397 of SEQ IDNO: 1) is Ala, Arg, Val, Ile, Met, His, Lys, Asp, Glu, Ser, Thr, Asn,Gln, Cys, Gly, Pro, Phe, Tyr, or Trp, and the amino acid at Mutated site5 (which corresponds to Phe420 of SEQ ID NO: 1) is Ala, Leu, Val, lie,Met, His, Lys, Asp, Glu, Ser, Thr, Asn, Gln, Cys, Gly, Pro, Arg, Tyr, orTrp.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110,111, 112, 113, 114, 115, 116, 117 577, 579, 581, 583, 585, 587, 589,591, 593, 595, 597, 599, 601, 603, 605, 607, 609, 611, 613, 615, 617,619, 621, 623, 625, 627, or 637, a variant, derivative, orthologue,paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Ala, and the amino acid at Mutatedsite 5 is Ala.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Ala, and the amino acid at Mutatedsite 5 is Leu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Ala, and the amino acid at Mutatedsite 5 is Val.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Ala, and the amino acid at Mutatedsite 5 is Ile.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Ala, and the amino acid at Mutatedsite 5 is Met.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Ala, and the amino acid at Mutatedsite 5 is His.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Ala, and the amino acid at Mutatedsite 5 is Lys.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Ala, and the amino acid at Mutatedsite 5 is Asp.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Ala, and the amino acid at Mutatedsite 5 is Glu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Ala, and the amino acid at Mutatedsite 5 is Ser.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Ala, and the amino acid at Mutatedsite 5 is Thr.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Ala, and the amino acid at Mutatedsite 5 is Asn.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Ala, and the amino acid at Mutatedsite 5 is Gln.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Ala, and the amino acid at Mutatedsite 5 is Cys.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Ala, and the amino acid at Mutatedsite 5 is Gly.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Ala, and the amino acid at Mutatedsite 5 is Pro.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Ala, and the amino acid at Mutatedsite 5 is Arg.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Ala, and the amino acid at Mutatedsite 5 is Tyr.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Ala, and the amino acid at Mutatedsite 5 is Trp.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which: theamino acid at Mutated site 4 is Arg, and the amino acid at Mutated site5 is Ala.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Arg, and the amino acid at Mutatedsite 5 is Leu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Arg, and the amino acid at Mutatedsite 5 is Val.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Arg, and the amino acid at Mutatedsite 5 is Ile.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Arg, and the amino acid at Mutatedsite 5 is Met.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Arg, and the amino acid at Mutatedsite 5 is His.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Arg, and the amino acid at Mutatedsite 5 is Lys.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Arg, and the amino acid at Mutatedsite 5 is Asp.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Arg, and the amino acid at Mutatedsite 5 is Glu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Arg, and the amino acid at Mutatedsite 5 is Ser.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Arg, and the amino acid at Mutatedsite 5 is Thr.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Arg, and the amino acid at Mutatedsite 5 is Asn.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Arg, and the amino acid at Mutatedsite 5 is Gln.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Arg, and the amino acid at Mutatedsite 5 is Cys.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Arg, and the amino acid at Mutatedsite 5 is Gly.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Arg, and the amino acid at Mutatedsite 5 is Pro.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Arg, and the amino acid at Mutatedsite 5 is Arg.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Arg, and the amino acid at Mutatedsite 5 is Tyr.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Arg, and the amino acid at Mutatedsite 5 is Trp.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Val, and the amino acid at Mutatedsite 5 is Ala.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Val, and the amino acid at Mutatedsite 5 is Leu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Val, and the amino acid at Mutatedsite 5 is Val.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Val, and the amino acid at Mutatedsite 5 is Ile.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which: theamino acid at Mutated site 4 is Val, and the amino acid at Mutated site5 is Met.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Val, and the amino acid at Mutatedsite 5 is His.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Val, and the amino acid at Mutatedsite 5 is Lys.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Val, and the amino acid at Mutatedsite 5 is Asp.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Val, and the amino acid at Mutatedsite 5 is Glu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Val, and the amino acid at Mutatedsite 5 is Ser.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Val, and the amino acid at Mutatedsite 5 is Thr.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Val, and the amino acid at Mutatedsite 5 is Asn.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Val, and the amino acid at Mutatedsite 5 is Gln.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Val, and the amino acid at Mutatedsite 5 is Cys.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Val, and the amino acid at Mutatedsite 5 is Gly.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Val, and the amino acid at Mutatedsite 5 is Pro.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Val, and the amino acid at Mutatedsite 5 is Arg.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Val, and the amino acid at Mutatedsite 5 is Tyr.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Val, and the amino acid at Mutatedsite 5 is Trp.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Ile, and the amino acid at Mutatedsite 5 is Ala.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is lie, and the amino acid at Mutatedsite 5 is Leu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is lie, and the amino acid at Mutatedsite 5 is Val.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is lie, and the amino acid at Mutatedsite 5 is Ile.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is lie, and the amino acid at Mutatedsite 5 is Met.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is lie, and the amino acid at Mutatedsite 5 is His.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is lie, and the amino acid at Mutatedsite 5 is Lys.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is lie, and the amino acid at Mutatedsite 5 is Asp.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which: theamino acid at Mutated site 4 is lie, and the amino acid at Mutated site5 is Glu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is lie, and the amino acid at Mutatedsite 5 is Ser.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is lie, and the amino acid at Mutatedsite 5 is Thr.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is lie, and the amino acid at Mutatedsite 5 is Asn.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is lie, and the amino acid at Mutatedsite 5 is Gln.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Ile, and the amino acid at Mutatedsite 5 is Cys.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Ile, and the amino acid at Mutatedsite 5 is Gly.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Ile, and the amino acid at Mutatedsite 5 is Pro.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is lie, and the amino acid at Mutatedsite 5 is Arg.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is lie, and the amino acid at Mutatedsite 5 is Tyr.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is lie, and the amino acid at Mutatedsite 5 is Trp.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Met, and the amino acid at Mutatedsite 5 is Ala.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Met, and the amino acid at Mutatedsite 5 is Leu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Met, and the amino acid at Mutatedsite 5 is Val.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Met, and the amino acid at Mutatedsite 5 is Ile.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Met, and the amino acid at Mutatedsite 5 is Met.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Met, and the amino acid at Mutatedsite 5 is His.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Met, and the amino acid at Mutatedsite 5 is Lys.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Met, and the amino acid at Mutatedsite 5 is Asp.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Met, and the amino acid at Mutatedsite 5 is Glu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Met, and the amino acid at Mutatedsite 5 is Ser.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Met, and the amino acid at Mutatedsite 5 is Thr.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Met, and the amino acid at Mutatedsite 5 is Asn.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Met, and the amino acid at Mutatedsite 5 is Gln.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Met, and the amino acid at Mutatedsite 5 is Cys.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Met, and the amino acid at Mutatedsite 5 is Gly.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Met, and the amino acid at Mutatedsite 5 is Pro.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which: theamino acid at Mutated site 4 is Met, and the amino acid at Mutated site5 is Arg.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Met, and the amino acid at Mutatedsite 5 is Tyr.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Met, and the amino acid at Mutatedsite 5 is Trp.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is His, and the amino acid at Mutatedsite 5 is Ala.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is His, and the amino acid at Mutatedsite 5 is Leu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is His, and the amino acid at Mutatedsite 5 is Val.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is His, and the amino acid at Mutatedsite 5 is Ile.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is His, and the amino acid at Mutatedsite 5 is Met.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is His, and the amino acid at Mutatedsite 5 is His.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is His, and the amino acid at Mutatedsite 5 is Lys.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is His, and the amino acid at Mutatedsite 5 is Asp.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is His, and the amino acid at Mutatedsite 5 is Glu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is His, and the amino acid at Mutatedsite 5 is Ser.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is His, and the amino acid at Mutatedsite 5 is Thr.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is His, and the amino acid at Mutatedsite 5 is Asn.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is His, and the amino acid at Mutatedsite 5 is Gln.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is His, and the amino acid at Mutatedsite 5 is Cys.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is His, and the amino acid at Mutatedsite 5 is Gly.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is His, and the amino acid at Mutatedsite 5 is Pro.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which: theamino acid at Mutated site 4 is His, and the amino acid at Mutated site5 is Arg.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is His, and the amino acid at Mutatedsite 5 is Tyr.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is His, and the amino acid at Mutatedsite 5 is Trp.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Lys, and the amino acid at Mutatedsite 5 is Ala.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Lys, and the amino acid at Mutatedsite 5 is Leu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Lys, and the amino acid at Mutatedsite 5 is Val.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Lys, and the amino acid at Mutatedsite 5 is Ile.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Lys, and the amino acid at Mutatedsite 5 is Met.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Lys, and the amino acid at Mutatedsite 5 is His.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Lys, and the amino acid at Mutatedsite 5 is Lys.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Lys, and the amino acid at Mutatedsite 5 is Asp.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Lys, and the amino acid at Mutatedsite 5 is Glu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Lys, and the amino acid at Mutatedsite 5 is Ser.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Lys, and the amino acid at Mutatedsite 5 is Thr.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Lys, and the amino acid at Mutatedsite 5 is Asn.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Lys, and the amino acid at Mutatedsite 5 is Gln.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Lys, and the amino acid at Mutatedsite 5 is Cys.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Lys, and the amino acid at Mutatedsite 5 is Gly.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Lys, and the amino acid at Mutatedsite 5 is Pro.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which: theamino acid at Mutated site 4 is Lys, and the amino acid at Mutated site5 is Arg.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Lys, and the amino acid at Mutatedsite 5 is Tyr.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Lys, and the amino acid at Mutatedsite 5 is Trp.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Asp, and the amino acid at Mutatedsite 5 is Ala.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Asp, and the amino acid at Mutatedsite 5 is Leu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Asp, and the amino acid at Mutatedsite 5 is Val.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Asp, and the amino acid at Mutatedsite 5 is Ile.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Asp, and the amino acid at Mutatedsite 5 is Met.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Asp, and the amino acid at Mutatedsite 5 is His.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Asp, and the amino acid at Mutatedsite 5 is Lys.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Asp, and the amino acid at Mutatedsite 5 is Asp.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Asp, and the amino acid at Mutatedsite 5 is Glu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Asp, and the amino acid at Mutatedsite 5 is Ser.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Asp, and the amino acid at Mutatedsite 5 is Thr.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Asp, and the amino acid at Mutatedsite 5 is Asn.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Asp, and the amino acid at Mutatedsite 5 is Gln.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Asp, and the amino acid at Mutatedsite 5 is Cys.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Asp, and the amino acid at Mutatedsite 5 is Gly.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Asp, and the amino acid at Mutatedsite 5 is Pro.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Asp, and the amino acid at Mutatedsite 5 is Arg.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Asp, and the amino acid at Mutatedsite 5 is Tyr.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Asp, and the amino acid at Mutatedsite 5 is Trp.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Glu, and the amino acid at Mutatedsite 5 is Ala.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which: theamino acid at Mutated site 4 is Glu, and the amino acid at Mutated site5 is Leu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Glu, and the amino acid at Mutatedsite 5 is Val.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Glu, and the amino acid at Mutatedsite 5 is Ile.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Glu, and the amino acid at Mutatedsite 5 is Met.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which: theamino acid at Mutated site 4 is Glu, and the amino acid at Mutated site5 is His.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Glu, and the amino acid at Mutatedsite 5 is Lys.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Glu, and the amino acid at Mutatedsite 5 is Asp.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Glu, and the amino acid at Mutatedsite 5 is Glu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Glu, and the amino acid at Mutatedsite 5 is Ser.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Glu, and the amino acid at Mutatedsite 5 is Thr.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Glu, and the amino acid at Mutatedsite 5 is Asn.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Glu, and the amino acid at Mutatedsite 5 is Gln.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Glu, and the amino acid at Mutatedsite 5 is Cys.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Glu, and the amino acid at Mutatedsite 5 is Gly.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Glu, and the amino acid at Mutatedsite 5 is Pro.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Glu, and the amino acid at Mutatedsite 5 is Arg.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Glu, and the amino acid at Mutatedsite 5 is Tyr.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Glu, and the amino acid at Mutatedsite 5 is Trp.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Ser, and the amino acid at Mutatedsite 5 is Ala.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Ser, and the amino acid at Mutatedsite 5 is Leu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Ser, and the amino acid at Mutatedsite 5 is Val.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Ser, and the amino acid at Mutatedsite 5 is Ile.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Ser, and the amino acid at Mutatedsite 5 is Met.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which: theamino acid at Mutated site 4 is Ser, and the amino acid at Mutated site5 is His.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Ser, and the amino acid at Mutatedsite 5 is Lys.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Ser, and the amino acid at Mutatedsite 5 is Asp.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Ser, and the amino acid at Mutatedsite 5 is Glu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Ser, and the amino acid at Mutatedsite 5 is Ser.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Ser, and the amino acid at Mutatedsite 5 is Thr.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Ser, and the amino acid at Mutatedsite 5 is Asn.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Ser, and the amino acid at Mutatedsite 5 is Gln.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Ser, and the amino acid at Mutatedsite 5 is Cys.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Ser, and the amino acid at Mutatedsite 5 is Gly.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Ser, and the amino acid at Mutatedsite 5 is Pro.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Ser, and the amino acid at Mutatedsite 5 is Arg.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Ser, and the amino acid at Mutatedsite 5 is Tyr.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Ser, and the amino acid at Mutatedsite 5 is Trp.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Thr, and the amino acid at Mutatedsite 5 is Ala.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Thr, and the amino acid at Mutatedsite 5 is Leu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Thr, and the amino acid at Mutatedsite 5 is Val.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Thr, and the amino acid at Mutatedsite 5 is Ile.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Thr, and the amino acid at Mutatedsite 5 is Met.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Thr, and the amino acid at Mutatedsite 5 is His.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Thr, and the amino acid at Mutatedsite 5 is Lys.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Thr, and the amino acid at Mutatedsite 5 is Asp.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Thr, and the amino acid at Mutatedsite 5 is Glu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Thr, and the amino acid at Mutatedsite 5 is Ser.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Thr, and the amino acid at Mutatedsite 5 is Thr.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Thr, and the amino acid at Mutatedsite 5 is Asn.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Thr, and the amino acid at Mutatedsite 5 is Gln.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Thr, and the amino acid at Mutatedsite 5 is Cys.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Thr, and the amino acid at Mutatedsite 5 is Gly.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Thr, and the amino acid at Mutatedsite 5 is Pro.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Thr, and the amino acid at Mutatedsite 5 is Arg.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Thr, and the amino acid at Mutatedsite 5 is Tyr.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Thr, and the amino acid at Mutatedsite 5 is Trp.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Asn, and the amino acid at Mutatedsite 5 is Ala.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Asn, and the amino acid at Mutatedsite 5 is Leu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Asn, and the amino acid at Mutatedsite 5 is Val.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Asn, and the amino acid at Mutatedsite 5 is Ile.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Asn, and the amino acid at Mutatedsite 5 is Met.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Asn, and the amino acid at Mutatedsite 5 is His.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Asn, and the amino acid at Mutatedsite 5 is Lys.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Asn, and the amino acid at Mutatedsite 5 is Asp.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Asn, and the amino acid at Mutatedsite 5 is Glu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Asn, and the amino acid at Mutatedsite 5 is Ser.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Asn, and the amino acid at Mutatedsite 5 is Thr.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Asn, and the amino acid at Mutatedsite 5 is Asn.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Asn, and the amino acid at Mutatedsite 5 is Gln.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Asn, and the amino acid at Mutatedsite 5 is Cys.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Asn, and the amino acid at Mutatedsite 5 is Gly.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Asn, and the amino acid at Mutatedsite 5 is Pro.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Asn, and the amino acid at Mutatedsite 5 is Arg.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Asn, and the amino acid at Mutatedsite 5 is Tyr.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Asn, and the amino acid at Mutatedsite 5 is Trp.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Gln, and the amino acid at Mutatedsite 5 is Ala.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Gln, and the amino acid at Mutatedsite 5 is Leu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Gln, and the amino acid at Mutatedsite 5 is Val.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Gln, and the amino acid at Mutatedsite 5 is Ile.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Gln, and the amino acid at Mutatedsite 5 is Met.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Gln, and the amino acid at Mutatedsite 5 is His.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Gln, and the amino acid at Mutatedsite 5 is Lys.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Gln, and the amino acid at Mutatedsite 5 is Asp.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Gln, and the amino acid at Mutatedsite 5 is Glu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Gln, and the amino acid at Mutatedsite 5 is Ser.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Gln, and the amino acid at Mutatedsite 5 is Thr.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Gln, and the amino acid at Mutatedsite 5 is Asn.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Gln, and the amino acid at Mutatedsite 5 is Gln.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110,111, 112, 113, 114, 115, 116, 117, 577, 579, 581, 583, 585, 587, 589,591, 593, 595, 597, 599, 601, 603, 605, 607, 609, 611, 613, 615, 617,619, 621, 623, 625, 627, or 637, a variant, derivative, orthologue,paralogue or homologue thereof, in which: the amino acid at Mutated site4 is Gln, and the amino acid at Mutated site 5 is Cys.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Gln, and the amino acid at Mutatedsite 5 is Gly.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Gln, and the amino acid at Mutatedsite 5 is Pro.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Gln, and the amino acid at Mutatedsite 5 is Arg.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Gln, and the amino acid at Mutatedsite 5 is Tyr.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Gln, and the amino acid at Mutatedsite 5 is Trp.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Cys, and the amino acid at Mutatedsite 5 is Ala.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Cys, and the amino acid at Mutatedsite 5 is Leu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Cys, and the amino acid at Mutatedsite 5 is Val.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Cys, and the amino acid at Mutatedsite 5 is Ile.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Cys, and the amino acid at Mutatedsite 5 is Met.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Cys, and the amino acid at Mutatedsite 5 is His.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Cys, and the amino acid at Mutatedsite 5 is Lys.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Cys, and the amino acid at Mutatedsite 5 is Asp.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Cys, and the amino acid at Mutatedsite 5 is Glu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Cys, and the amino acid at Mutatedsite 5 is Ser.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Cys, and the amino acid at Mutatedsite 5 is Thr.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Cys, and the amino acid at Mutatedsite 5 is Asn.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Cys, and the amino acid at Mutatedsite 5 is Gln.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Cys, and the amino acid at Mutatedsite 5 is Cys.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Cys, and the amino acid at Mutatedsite 5 is Gly.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Cys, and the amino acid at Mutatedsite 5 is Pro.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Cys, and the amino acid at Mutatedsite 5 is Arg.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Cys, and the amino acid at Mutatedsite 5 is Tyr.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Cys, and the amino acid at Mutatedsite 5 is Trp.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Gly, and the amino acid at Mutatedsite 5 is Ala.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Gly, and the amino acid at Mutatedsite 5 is Leu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Gly, and the amino acid at Mutatedsite 5 is Val.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Gly, and the amino acid at Mutatedsite 5 is Ile.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Gly, and the amino acid at Mutatedsite 5 is Met.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Gly, and the amino acid at Mutatedsite 5 is His.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Gly, and the amino acid at Mutatedsite 5 is Lys.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Gly, and the amino acid at Mutatedsite 5 is Asp.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Gly, and the amino acid at Mutatedsite 5 is Glu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Gly, and the amino acid at Mutatedsite 5 is Ser.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Gly, and the amino acid at Mutatedsite 5 is Thr.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Gly, and the amino acid at Mutatedsite 5 is Asn.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Gly, and the amino acid at Mutatedsite 5 is Gln.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Gly, and the amino acid at Mutatedsite 5 is Cys.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Gly, and the amino acid at Mutatedsite 5 is Gly.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Gly, and the amino acid at Mutatedsite 5 is Pro.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Gly, and the amino acid at Mutatedsite 5 is Arg.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Gly, and the amino acid at Mutatedsite 5 is Tyr.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Gly, and the amino acid at Mutatedsite 5 is Trp.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Pro, and the amino acid at Mutatedsite 5 is Ala.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Pro, and the amino acid at Mutatedsite 5 is Leu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which: theamino acid at Mutated site 4 is Pro, and the amino acid at Mutated site5 is Val.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Pro, and the amino acid at Mutatedsite 5 is Ile.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Pro, and the amino acid at Mutatedsite 5 is Met.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Pro, and the amino acid at Mutatedsite 5 is His.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Pro, and the amino acid at Mutatedsite 5 is Lys.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Pro, and the amino acid at Mutatedsite 5 is Asp.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Pro, and the amino acid at Mutatedsite 5 is Glu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Pro, and the amino acid at Mutatedsite 5 is Ser.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Pro, and the amino acid at Mutatedsite 5 is Thr.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Pro, and the amino acid at Mutatedsite 5 is Asn.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Pro, and the amino acid at Mutatedsite 5 is Gln.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Pro, and the amino acid at Mutatedsite 5 is Cys.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Pro, and the amino acid at Mutatedsite 5 is Gly.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Pro, and the amino acid at Mutatedsite 5 is Pro.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Pro, and the amino acid at Mutatedsite 5 is Arg.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Pro, and the amino acid at Mutatedsite 5 is Tyr.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Pro, and the amino acid at Mutatedsite 5 is Trp.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Phe, and the amino acid at Mutatedsite 5 is Ala.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Phe, and the amino acid at Mutatedsite 5 is Leu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Phe, and the amino acid at Mutatedsite 5 is Val.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Phe, and the amino acid at Mutatedsite 5 is Ile.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Phe, and the amino acid at Mutatedsite 5 is Met.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Phe, and the amino acid at Mutatedsite 5 is His.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Phe, and the amino acid at Mutatedsite 5 is Lys.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Phe, and the amino acid at Mutatedsite 5 is Asp.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Phe, and the amino acid at Mutatedsite 5 is Glu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Phe, and the amino acid at Mutatedsite 5 is Ser.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Phe, and the amino acid at Mutatedsite 5 is Thr.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Phe, and the amino acid at Mutatedsite 5 is Asn.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Phe, and the amino acid at Mutatedsite 5 is Gln.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Phe, and the amino acid at Mutatedsite 5 is Cys.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Phe, and the amino acid at Mutatedsite 5 is Gly.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Phe, and the amino acid at Mutatedsite 5 is Pro.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Phe, and the amino acid at Mutatedsite 5 is Arg.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Phe, and the amino acid at Mutatedsite 5 is Tyr.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Phe, and the amino acid at Mutatedsite 5 is Trp.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Tyr, and the amino acid at Mutatedsite 5 is Ala.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Tyr, and the amino acid at Mutatedsite 5 is Leu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Tyr, and the amino acid at Mutatedsite 5 is Val.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Tyr, and the amino acid at Mutatedsite 5 is Ile.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Tyr, and the amino acid at Mutatedsite 5 is Met.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Tyr, and the amino acid at Mutatedsite 5 is His.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Tyr, and the amino acid at Mutatedsite 5 is Lys.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Tyr, and the amino acid at Mutatedsite 5 is Asp.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Tyr, and the amino acid at Mutatedsite 5 is Glu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Tyr, and the amino acid at Mutatedsite 5 is Ser.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Tyr, and the amino acid at Mutatedsite 5 is Thr.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Tyr, and the amino acid at Mutatedsite 5 is Asn.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Tyr, and the amino acid at Mutatedsite 5 is Gln.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Tyr, and the amino acid at Mutatedsite 5 is Cys.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Tyr, and the amino acid at Mutatedsite 5 is Gly.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Tyr, and the amino acid at Mutatedsite 5 is Pro.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Tyr, and the amino acid at Mutatedsite 5 is Arg.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Tyr, and the amino acid at Mutatedsite 5 is Tyr.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Tyr, and the amino acid at Mutatedsite 5 is Trp.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Trp, and the amino acid at Mutatedsite 5 is Ala.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Trp, and the amino acid at Mutatedsite 5 is Leu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Trp, and the amino acid at Mutatedsite 5 is Val.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Trp, and the amino acid at Mutatedsite 5 is Ile.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Trp, and the amino acid at Mutatedsite 5 is Met.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Trp, and the amino acid at Mutatedsite 5 is His.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Trp, and the amino acid at Mutatedsite 5 is Lys.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Trp, and the amino acid at Mutatedsite 5 is Asp.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Trp, and the amino acid at Mutatedsite 5 is Glu.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Trp, and the amino acid at Mutatedsite 5 is Ser.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Trp, and the amino acid at Mutatedsite 5 is Thr.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Trp, and the amino acid at Mutatedsite 5 is Asn.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Trp, and the amino acid at Mutatedsite 5 is Gln.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Trp, and the amino acid at Mutatedsite 5 is Cys.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Trp, and the amino acid at Mutatedsite 5 is Gly.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Trp, and the amino acid at Mutatedsite 5 is Pro.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Trp, and the amino acid at Mutatedsite 5 is Arg.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Trp, and the amino acid at Mutatedsite 5 is Tyr.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 4 is Trp, and the amino acid at Mutatedsite 5 is Trp.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 3 is other than Gly, is preferably Arg.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 6 is other than Gly, is preferably Ala.

In another preferred embodiment, the mutated PPO comprises a sequence ofSEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637, a variant,derivative, orthologue, paralogue or homologue thereof, in which:

the amino acid at Mutated site 7 is other than Leu, is preferably Phe.

It will be within the knowledge of the skilled artisan to identifyconserved regions and motifs shared between the homologues, orthologuesand paralogues of PPO polypeptides comprising SEQ ID NO: 1, 2, 3, 4, 5,6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24,25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42,43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60,61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78,79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96,97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111,112, 113, 114, 115, 116, 117, 577, 579, 581, 583, 585, 587, 589, 591,593, 595, 597, 599, 601, 603, 605, 607, 609, 611, 613, 615, 617, 619,621, 623, 625, 627, or 637. Having identified such conserved regionsthat may represent suitable binding motifs, amino acids corresponding tothe amino acids listed in Table 2a and 2b can be chosen to besubstituted by any other amino acid, preferably by the amino acidslisted under mutated sites 1, 2, 3, 4, or 5.

Accordingly, preferred motifs shared between the homologues, orthologuesand paralogues of PPO polypeptides described above are Motif 1:SQ[N/K/H]KRYI, wherein the Arg at position 5 within said motif issubstituted by Leu, Ala, Val, lie, Met, Tyr, Gly, Asn, Cys, Phe, Ser,Thr, Gln, or His; Motif 2: TLGTLFSS, wherein the Leu at position 2within said motif is substituted by Ala, Arg, Val, lie, Met, His, Lys,Asp, Glu, Ser, Thr, Asn, Gln, Cys, Gly, Pro, Phe, Tyr, or Trp; and/orwherein the Gly at position 3 within said motif is substituted by Ala,Arg, Val, Ile, Met, His, Lys, Asp, Glu, Ser, Thr, Asn, Gln, Cys, Leu,Pro, Phe, Tyr, or Trp; and/or wherein the Leu at position 5 within saidmotif is substituted by Ala, Arg, Val, le, Met, His, Lys, Asp, Glu, Ser,Thr, Asn, Gln, Cys, Gly, Pro, Phe, Tyr, or Trp; Motif 3:[F/Y]TTF[V/I]GG, wherein the Phe at position 4 within said motif issubstituted by Ala, Leu, Val, lie, Met, His, Lys, Asp, Glu, Ser, Thr,Asn, Gln, Cys, Gly, Pro, Arg, Tyr, or Trp.

Further examples of such homologues, orthologues and paralogues are PPOpolypeptides comprising the amino acid sequence of SEQ ID NO: 577, 579,581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607,609, 611, 613, 615, 617, 619, 621, 623, 625, 627, or 637.

In addition, the present invention refers to a method for identifying auracilpyridine herbicide by using a herbicide tolerant PPO polypeptideas defined SUPRA.

Said method comprises the steps of:

-   -   a) generating a transgenic cell or plant comprising a nucleic        acid encoding a mutated PPO, wherein the mutated PPO is        expressed;    -   b) applying a uracilpyridine herbicide to the transgenic cell or        plant of a) and to a control cell or plant of the same variety;    -   c) determining the growth or the viability of the transgenic        cell or plant and the control cell or plant after application of        said uracilpyridine herbicide, and    -   d) selecting “uracilpyridine herbicides” which confer reduced        growth to the control cell or plant as compared to the growth of        the transgenic cell or plant.

By “control cell” or “similar, wild-type, plant, plant tissue, plantcell or host cell” is intended a plant, plant tissue, plant cell, orhost cell, respectively, that lacks the herbicide-resistancecharacteristics and/or particular polynucleotide of the invention thatare disclosed herein. The use of the term “wild-type” is not, therefore,intended to imply that a plant, plant tissue, plant cell, or other hostcell lacks recombinant DNA in its genome, and/or does not possessherbicide-resistant characteristics that are different from thosedisclosed herein.

Another object refers to a method of identifying a nucleotide sequenceencoding a mutated PPO which is resistant or tolerant to auracilpyridine herbicide, the method comprising:

-   -   a) generating a library of mutated PPO-encoding nucleic acids,    -   b) screening a population of the resulting mutated PPO-encoding        nucleic acids by expressing each of said nucleic acids in a cell        or plant and treating said cell or plant with a uracilpyridine        herbicide,    -   c) comparing the uracilpyridine herbicide-tolerance levels        provided by said population of mutated PPO encoding nucleic        acids with the uracilpyridine herbicide-tolerance level provided        by a control PPO-encoding nucleic acid,    -   d) selecting at least one mutated PPO-encoding nucleic acid that        provides a significantly increased level of tolerance to a        uracilpyridine herbicide as compared to that provided by the        control PPO-encoding nucleic acid.

In a preferred embodiment, the mutated PPO-encoding nucleic acidselected in step d) provides at least 2-fold as much resistance ortolerance of a cell or plant to a uracilpyridine herbicide as comparedto that provided by the control PPO-encoding nucleic acid.

In a further preferred embodiment, the mutated PPO-encoding nucleic acidselected in step d) provides at least 2-fold, at least 5-fold, at least10-fold, at least 20-fold, at least 50-fold, at least 100-fold, at least500-fold, as much resistance or tolerance of a cell or plant to auracilpyridine herbicide as compared to that provided by the controlPPO-encoding nucleic acid.

The resistance or tolerance can be determined by generating a transgenicplant or host cell, preferably a plant cell, comprising a nucleic acidsequence of the library of step a) and comparing said transgenic plantwith a control plant or host cell, preferably a plant cell.

Another object refers to a method of identifying a plant or algaecontaining a nucleic acid comprising a nucleotide sequence encoding awild-type or mutated PPO which is resistant or tolerant to auracilpyridine herbicide, the method comprising:

-   -   a) identifying an effective amount of a uracilpyridine herbicide        in a culture of plant cells or green algae that leads to death        of said cells.    -   b) treating said plant cells or green algae with a mutagenizing        agent,    -   c) contacting said mutagenized cells population with an        effective amount of uracilpyridine herbicide, identified in a),    -   d) selecting at least one cell surviving these test conditions,    -   e) PCR-amplification and sequencing of PPO genes from cells        selected in d) and comparing such sequences to wild-type PPO        gene sequences, respectively.

In a preferred embodiment, said mutagenizing agent isethylmethanesulfonate (EMS). Many methods well known to the skilledartisan are available for obtaining suitable candidate nucleic acids foridentifying a nucleotide sequence encoding a mutated PPO from a varietyof different potential source organisms including microbes, plants,fungi, algae, mixed cultures etc. as well as environmental sources ofDNA such as soil. These methods include inter alia the preparation ofcDNA or genomic DNA libraries, the use of suitably degenerateoligonucleotide primers, the use of probes based upon known sequences orcomplementation assays (for example, for growth upon tyrosine) as wellas the use of mutagenesis and shuffling in order to provide recombinedor shuffled mutated PPO-encoding sequences.

Nucleic acids comprising candidate and control PPO encoding sequencescan be expressed in yeast, in a bacterial host strain, in an alga or ina higher plant such as tobacco or Arabidopsis and the relative levels ofinherent tolerance of the PPO encoding sequences screened according to avisible indicator phenotype of the transformed strain or plant in thepresence of different concentrations of the selected uracilpyridineherbicide. Dose responses and relative shifts in dose responsesassociated with these indicator phenotypes (formation of brown color,growth inhibition, herbicidal effect etc) are conveniently expressed interms, for example, of GR50 (concentration for 50% reduction of growth)or MIC (minimum inhibitory concentration) values where increases invalues correspond to increases in inherent tolerance of the expressedPPO. For example, in a relatively rapid assay system based upontransformation of a bacterium such as E. coli, each mutated PPO encodingsequence may be expressed, for example, as a DNA sequence underexpression control of a controllable promoter such as the lacZ promoterand taking suitable account, for example by the use of synthetic DNA, ofsuch issues as codon usage in order to obtain as comparable a level ofexpression as possible of different PPO sequences. Such strainsexpressing nucleic acids comprising alternative candidate PPO sequencesmay be plated out on different concentrations of the selecteduracilpyridine herbicide in, optionally, a tyrosine supplemented mediumand the relative levels of inherent tolerance of the expressed PPOenzymes estimated on the basis of the extent and MIC for inhibition ofthe formation of the brown, ochronotic pigment.

In another embodiment, candidate nucleic acids are transformed intoplant material to generate a transgenic plant, regenerated intomorphologically normal fertile plants which are then measured fordifferential tolerance to selected uracilpyridine herbicides asdescribed in the Example section hereinafter. Many suitable methods fortransformation using suitable selection markers such as kanamycin,binary vectors such as from Agrobacterium and plant regeneration as, forexample, from tobacco leaf discs are well known in the art. Optionally,a control population of plants is likewise transformed with a nucleicacid expressing the control PPO. Alternatively, an untransformed dicotplant such as Arabidopsis or Tobacco can be used as a control sincethis, in any case, expresses its own endogenous PPO. The average, anddistribution, of herbicide tolerance levels of a range of primary planttransformation events or their progeny to uracilpyridine herbicidesdescribed supra are evaluated in the normal manner based upon plantdamage, meristematic bleaching symptoms etc. at a range of differentconcentrations of herbicides. These data can be expressed in terms of,for example, GR50 values derived from dose/response curves having “dose”plotted on the x-axis and “percentage kill”, “herbicidal effect”,“numbers of emerging green plants” etc. plotted on the y-axis whereincreased GR50 values correspond to increased levels of inherenttolerance of the expressed PPO. Herbicides can suitably be appliedpre-emergence or post-emergence.

In another embodiment, the invention refers to a plant cell transformedby a nucleic acid encoding a herbicide tolerant PPO polypeptidedisclosed herein or to a plant cell which has been mutated to obtain aplant expressing a nucleic acid encoding a mutated PPO polypeptideaccording to the present invention, wherein expression of the nucleicacid in the plant cell results in increased resistance or tolerance to auracilpyridine herbicide as compared to a wild type variety of the plantcell.

The term “expression/expressing” or “gene expression” means thetranscription of a specific gene or specific genes or specific geneticconstruct. The term “expression” or “gene expression” in particularmeans the transcription of a gene or genes or genetic construct intostructural RNA (rRNA, tRNA) or mRNA with or without subsequenttranslation of the latter into a protein. The process includestranscription of DNA and processing of the resulting mRNA product.

To obtain the desired effect, i.e. plants that are tolerant or resistantto the uracilpyridine herbicide derivative herbicide of the presentinvention, it will be understood that the at least one nucleic acid is“over-expressed” by methods and means known to the person skilled in theart.

The term “increased expression” or “overexpression” as used herein meansany form of expression that is additional to the original wild-typeexpression level. Methods for increasing expression of genes or geneproducts are well documented in the art and include, for example,overexpression driven by appropriate promoters, the use of transcriptionenhancers or translation enhancers. Isolated nucleic acids which serveas promoter or enhancer elements may be introduced in an appropriateposition (typically upstream) of a non-heterologous form of apolynucleotide so as to upregulate expression of a nucleic acid encodingthe polypeptide of interest. For example, endogenous promoters may bealtered in vivo by mutation, deletion, and/or substitution (see, Kmiec,U.S. Pat. No. 5,565,350; Zarling et al., WO9322443), or isolatedpromoters may be introduced into a plant cell in the proper orientationand distance from a gene of the present invention so as to control theexpression of the gene.

If polypeptide expression is desired, it is generally desirable toinclude a polyadenylation region at the 3′-end of a polynucleotidecoding region. The polyadenylation region can be derived from thenatural gene, from a variety of other plant genes, or from T-DNA. The 3′end sequence to be added may be derived from, for example, the nopalinesynthase or octopine synthase genes, or alternatively from another plantgene, or less preferably from any other eukaryotic gene.

An intron sequence may also be added to the 5′ untranslated region (UTR)or the coding sequence of the partial coding sequence to increase theamount of the mature message that accumulates in the cytosol. Inclusionof a spliceable intron in the transcription unit in both plant andanimal expression constructs has been shown to increase gene expressionat both the mRNA and protein levels up to 1000-fold (Buchman and Berg(1988) Mol. Cell biol. 8: 4395-4405; Callis et al. (1987) Genes Dev1:1183-1200). Such intron enhancement of gene expression is typicallygreatest when placed near the 5′ end of the transcription unit. Use ofthe maize introns Adh1-S intron 1, 2, and 6, the Bronze-1 intron areknown in the art. For general information see: The Maize Handbook,Chapter 116, Freeling and Walbot, Eds., Springer, N.Y. (1994)

The term “introduction” or “transformation” as referred to hereinencompasses the transfer of an exogenous polynucleotide into a hostcell, irrespective of the method used for transfer. Plant tissue capableof subsequent clonal propagation, whether by organogenesis orembryogenesis, may be transformed with a genetic construct of thepresent invention and a whole plant regenerated there from. Theparticular tissue chosen will vary depending on the clonal propagationsystems available for, and best suited to, the particular species beingtransformed. Exemplary tissue targets include leaf disks, pollen,embryos, cotyledons, hypocotyls, megagametophytes, callus tissue,existing meristematic tissue (e.g., apical meristem, axillary buds, androot meristems), and induced meristem tissue (e.g., cotyledon meristemand hypocotyl meristem). The polynucleotide may be transiently or stablyintroduced into a host cell and may be maintained non-integrated, forexample, as a plasmid. Alternatively, it may be integrated into the hostgenome. The resulting transformed plant cell may then be used toregenerate a transformed plant in a manner known to persons skilled inthe art.

The transfer of foreign genes into the genome of a plant is calledtransformation. Transformation of plant species is now a fairly routinetechnique. Advantageously, any of several transformation methods may beused to introduce the gene of interest into a suitable ancestor cell.The methods described for the transformation and regeneration of plantsfrom plant tissues or plant cells may be utilized for transient or forstable transformation. Transformation methods include the use ofliposomes, electroporation, chemicals that increase free DNA uptake,injection of the DNA directly into the plant, particle gun bombardment,transforrmation using viruses or pollen and microprojection.

Methods may be selected from the calcium/polyethylene glycol method forprotoplasts (Krens, F. A. et al., (1982) Nature 296, 72-74; Negrutiu Iet al. (1987) Plant Mol Biol 8: 363-373); electroporation of protoplasts(Shillito R. D. et al. (1985) Bio/Technol 3, 1099-1102); microinjectioninto plant material (Crossway A et al., (1986) Mol. Gen Genet 202:179-185); DNA or RNA-coated particle bombardment (Klein T M et al.,(1987) Nature 327: 70) infection with (non-integrative) viruses and thelike. Transgenic plants, including transgenic crop plants, arepreferably produced via Agrobacterium-mediated transformation. Anadvantageous transformation method is the transformation in planta. Tothis end, it is possible, for example, to allow the agrobacteria to acton plant seeds or to inoculate the plant meristem with agrobacteria. Ithas proved particularly expedient in accordance with the invention toallow a suspension of transformed agrobacteria to act on the intactplant or at least on the flower primordia. The plant is subsequentlygrown on until the seeds of the treated plant are obtained (Clough andBent, Plant J. (1998) 16, 735-743). Methods for Agrobacterium-mediatedtransformation of rice include well known methods for ricetransformation, such as those described in any of the following:European patent application EP 1198985 A1, Aldemita and Hodges (Planta199: 612-617, 1996); Chan et al. (Plant Mol Biol 22 (3): 491-506, 1993),Hiei et al. (Plant J 6 (2): 271-282, 1994), which disclosures areincorporated by reference herein as if fully set forth. In the case ofcorn transformation, the preferred method is as described in eitherIshida et al. (Nat. Biotechnol 14(6): 745-50, 1996) or Frame et al.(Plant Physiol 129(1): 13-22, 2002), which disclosures are incorporatedby reference herein as if fully set forth. Said methods are furtherdescribed by way of example in B. Jenes et al., Techniques for GeneTransfer, in: Transgenic Plants, Vol. 1, Engineering and Utilization,eds. S. D. Kung and R. Wu, Academic Press (1993) 128-143 and in PotrykusAnnu. Rev. Plant Physiol. Plant Molec. Biol. 42 (1991) 205-225). Thenucleic acids or the construct to be expressed is preferably cloned intoa vector, which is suitable for transforming Agrobacterium tumefaciens,for example pBin19 (Bevan et al., Nucl. Acids Res. 12 (1984) 8711).Agrobacteria transformed by such a vector can then be used in knownmanner for the transformation of plants, such as plants used as a model,like Arabidopsis (Arabidopsis thaliana is within the scope of thepresent invention not considered as a crop plant), or crop plants suchas, by way of example, tobacco plants, for example by immersing bruisedleaves or chopped leaves in an agrobacterial solution and then culturingthem in suitable media. The transformation of plants by means ofAgrobacterium tumefaciens is described, for example, by Höfgen andWillmitzer in Nucl. Acid Res. (1988) 16, 9877 or is known inter ala fromF. F. White, Vectors for Gene Transfer in Higher Plants; in TransgenicPlants, Vol. 1, Engineering and Utilization, eds. S. D. Kung and R. Wu,Academic Press, 1993, pp. 15-38.

In addition to the transformation of somatic cells, which then have tobe regenerated into intact plants, it is also possible to transform thecells of plant meristems and in particular those cells which developinto gametes. In this case, the transformed gametes follow the naturalplant development, giving rise to transgenic plants. Thus, for example,seeds of Arabidopsis are treated with agrobacteria and seeds areobtained from the developing plants of which a certain proportion istransformed and thus transgenic [Feldman, K A and Marks M D (1987). MolGen Genet 208:274-289; Feldmann K (1992). In: C Koncz, N-H Chua and JShell, eds, Methods in Arabidopsis Research. Word Scientific, Singapore,pp. 274-289]. Alternative methods are based on the repeated removal ofthe inflorescences and incubation of the excision site in the center ofthe rosette with transformed agrobacteria, whereby transformed seeds canlikewise be obtained at a later point in time (Chang (1994). Plant J. 5:551-558; Katavic (1994). Mol Gen Genet, 245: 363-370). However, anespecially effective method is the vacuum infiltration method with itsmodifications such as the “floral dip” method. In the case of vacuuminfiltration of Arabidopsis, intact plants under reduced pressure aretreated with an agrobacterial suspension [Bechthold, N (1993). C R AcadSci Paris Life Sci, 316: 1194-1199], while in the case of the “floraldip” method the developing floral tissue is incubated briefly with asurfactant-treated agrobacterial suspension [Clough, S J and Bent A F(1998) The Plant J. 16, 735-743]. A certain proportion of transgenicseeds are harvested in both cases, and these seeds can be distinguishedfrom non-transgenic seeds by growing under the above-described selectiveconditions. In addition the stable transformation of plastids is ofadvantages because plastids are inherited maternally is most cropsreducing or eliminating the risk of transgene flow through pollen. Thetransformation of the chloroplast genome is generally achieved by aprocess which has been schematically displayed in Klaus et al., 2004[Nature Biotechnology 22 (2), 225-229]. Briefly the sequences to betransformed are cloned together with a selectable marker gene betweenflanking sequences homologous to the chloroplast genome. Thesehomologous flanking sequences direct site specific integration into theplastome. Plastidal transformation has been described for many differentplant species and an overview is given in Bock (2001) Transgenicplastids in basic research and plant biotechnology. J Mol Biol. 2001Sep. 21; 312 (3):425-38 or Maliga, P (2003) Progress towardscommercialization of plastid transformation technology. TrendsBiotechnol. 21, 20-28. Further biotechnological progress has recentlybeen reported in form of marker free plastid transformants, which can beproduced by a transient co-integrated maker gene (Klaus et al., 2004,Nature Biotechnology 22(2), 225-229). The genetically modified plantcells can be regenerated via all methods with which the skilled workeris familiar. Suitable methods can be found in the abovementionedpublications by S. D. Kung and R. Wu, Potrykus or Höfgen and Willmitzer.

Generally after transformation, plant cells or cell groupings areselected for the presence of one or more markers which are encoded byplant-expressible genes co-transferred with the gene of interest,following which the transformed material is regenerated into a wholeplant. To select transformed plants, the plant material obtained in thetransformation is, as a rule, subjected to selective conditions so thattransformed plants can be distinguished from untransformed plants. Forexample, the seeds obtained in the above-described manner can be plantedand, after an initial growing period, subjected to a suitable selectionby spraying. A further possibility consists in growing the seeds, ifappropriate after sterilization, on agar plates using a suitableselection agent so that only the transformed seeds can grow into plants.Alternatively, the transformed plants are screened for the presence of aselectable marker such as the ones described above.

Following DNA transfer and regeneration, putatively transformed plantsmay also be evaluated, for instance using Southern analysis, for thepresence of the gene of interest, copy number and/or genomicorganisation. Alternatively or additionally, expression levels of thenewly introduced DNA may be monitored using Northern and/or Westernanalysis, both techniques being well known to persons having ordinaryskill in the art.

The generated transformed plants may be propagated by a variety ofmeans, such as by clonal propagation or classical breeding techniques.For example, a first generation (or T1) transformed plant may be selfedand homozygous second-generation (or T2) transformants selected, and theT2 plants may then further be propagated through classical breedingtechniques. The generated transformed organisms may take a variety offorms. For example, they may be chimeras of transformed cells andnon-transformed cells; clonal transformants (e.g., all cells transformedto contain the expression cassette); grafts of transformed anduntransformed tissues (e.g., in plants, a transformed rootstock graftedto an untransformed scion).

Preferably, the wild-type or mutated PPO nucleic acid comprises apolynucleotide sequence selected from the group consisting of: a) apolynucleotide encoding a polypeptide as shown in SEQ ID NO: 1, 2, 3, 4,5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41,42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59,60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77,78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95,96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110,111, 112, 113, 114, 115, 116, 117, 577, 579, 581, 583, 585, 587, 589,591, 593, 595, 597, 599, 601, 603, 605, 607, 609, 611, 613, 615, 617,619, 621, 623, 625, 627, or 637,or a variant or derivative thereof; b) apolynucleotide comprising at least 60 consecutive nucleotides of any ofa); and c) a polynucleotide complementary to the polynucleotide of anyof a) through b).

Preferably, the expression of the nucleic acid in the plant results inthe plant's increased resistance to uracilpyridine herbicide as comparedto a wild type variety of the plant.

In another embodiment, the invention refers to a plant, preferably atransgenic plant, comprising a plant cell according to the presentinvention, wherein expression of the nucleic acid in the plant resultsin the plant's increased resistance to uracilpyridine herbicide ascompared to a wild type variety of the plant.

The plants described herein can be either transgenic crop plants ornon-transgenic plants. For the purposes of the invention, “transgenic”,“transgene” or “recombinant” means with regard to, for example, anucleic acid sequence, an expression cassette, gene construct or avector comprising the nucleic acid sequence or an organism transformedwith the nucleic acid sequences, expression cassettes or vectorsaccording to the invention, all those constructions brought about byrecombinant methods in which either

-   -   (a) the nucleic acid sequences encoding proteins useful in the        methods of the invention, or    -   (b) genetic control sequence(s) which is operably linked with        the nucleic acid sequence according to the invention, for        example a promoter, or    -   (c) a) and b)

are not located in their natural genetic environment or have beenmodified by recombinant methods, it being possible for the modificationto take the form of, for example, a substitution, addition, deletion,inversion or insertion of one or more nucleotide residues in order toallow for the expression of the mutated PPO of the present invention.The natural genetic environment is understood as meaning the naturalgenomic or chromosomal locus in the original plant or the presence in agenomic library. In the case of a genomic library, the natural geneticenvironment of the nucleic acid sequence is preferably retained, atleast in part. The environment flanks the nucleic acid sequence at leaston one side and has a sequence length of at least 50 bp, preferably atleast 500 bp, especially preferably at least 1000 bp, most preferably atleast 5000 bp. A naturally occurring expression cassette—for example thenaturally occurring combination of the natural promoter of the nucleicacid sequences with the corresponding nucleic acid sequence encoding apolypeptide useful in the methods of the present invention, as definedabove—becomes a transgenic expression cassette when this expressioncassette is modified by non-natural, synthetic (“artificial”) methodssuch as, for example, mutagenic treatment. Suitable methods aredescribed, for example, in U.S. Pat. No. 5,565,350 or WO 00/15815.

A transgenic plant for the purposes of the invention is thus understoodas meaning, as above, that the nucleic acids of the invention are not attheir natural locus in the genome of said plant, it being possible forthe nucleic acids to be expressed homologously or heterologously.However, as mentioned, transgenic also means that, while the nucleicacids according to the invention or used in the inventive method are attheir natural position in the genome of a plant, the sequence has beenmodified with regard to the natural sequence, and/or that the regulatorysequences of the natural sequences have been modified. Transgenic ispreferably understood as meaning the expression of the nucleic acidsaccording to the invention at an unnatural locus in the genome, i.e.homologous or, preferably, heterologous expression of the nucleic acidstakes place. Preferred transgenic plants are mentioned herein.Furthermore, the term “transgenic” refers to any plant, plant cell,callus, plant tissue, or plant part, that contains all or part of atleast one recombinant polynucleotide. In many cases, all or part of therecombinant polynucleotide is stably integrated into a chromosome orstable extra-chromosomal element, so that it is passed on to successivegenerations. For the purposes of the invention, the term “recombinantpolynucleotide” refers to a polynucleotide that has been altered,rearranged, or modified by genetic engineering. Examples include anycloned polynucleotide, or polynucleotides, that are linked or joined toheterologous sequences. The term “recombinant” does not refer toalterations of polynucleotides that result from naturally occurringevents, such as spontaneous mutations, or from non-spontaneousmutagenesis followed by selective breeding.

Plants containing mutations arising due to non-spontaneous mutagenesisand selective breeding are referred to herein as non-transgenic plantsand are included in the present invention. In embodiments wherein theplant is transgenic and comprises multiple mutated PPO nucleic acids,the nucleic acids can be derived from different genomes or from the samegenome. Alternatively, in embodiments wherein the plant isnon-transgenic and comprises multiple mutated PPO nucleic acids, thenucleic acids are located on different genomes or on the same genome.

As used herein, “mutagenized” refers to an organism or DNA thereofhaving alteration(s) in the biomolecular sequence of its native geneticmaterial as compared to the sequence of the genetic material of acorresponding wild-type organism or DNA, wherein the alteration(s) ingenetic material were induced and/or selected by human action. Methodsof inducing mutations can induce mutations in random positions in thegenetic material or can induce mutations in specific locations in thegenetic material (i.e., can be directed mutagenesis techniques), such asby use of a genoplasty technique.

In certain embodiments, the present invention involvesherbicide-resistant plants that are produced by mutation breeding. Suchplants comprise a polynucleotide encoding a mutated PPO and are tolerantto one or more uracilpyridine herbicides. Such methods can involve, forexample, exposing the plants or seeds to a mutagen, particularly achemical mutagen such as, for example, ethyl methanesulfonate (EMS) andselecting for plants that have enhanced tolerance to at least one ormore uracilpyridine herbicide.

However, the present invention is not limited to herbicide-tolerantplants that are produced by a mutagenesis method involving the chemicalmutagen EMS. Any mutagenesis method known in the art may be used toproduce the herbicide-resistant plants of the present invention. Suchmutagenesis methods can involve, for example, the use of any one or moreof the following mutagens: radiation, such as X-rays, Gamma rays (e.g.,cobalt 60 or cesium 137), neutrons, (e.g., product of nuclear fission byuranium 235 in an atomic reactor), Beta radiation (e.g., emitted fromradioisotopes such as phosphorus 32 or carbon 14), and ultravioletradiation (preferably from 2500 to 2900 nm), and chemical mutagens suchas base analogues (e.g., 5-bromo-uracil), related compounds (e.g.,8-ethoxy caffeine), antibiotics (e.g., streptonigrin), alkylating agents(e.g., sulfur mustards, nitrogen mustards, epoxides, ethylenamines,sulfates, sulfonates, sulfones, lactones), azide, hydroxylamine, nitrousacid, or acridines. Herbicide-resistant plants can also be produced byusing tissue culture methods to select for plant cells comprisingherbicide-resistance mutations and then regenerating herbicide-resistantplants therefrom. See, for example, U.S. Pat. Nos. 5,773,702 and5,859,348, both of which are herein incorporated in their entirety byreference. Further details of mutation breeding can be found in“Principals of Cultivar Development” Fehr, 1993 Macmillan PublishingCompany the disclosure of which is incorporated herein by reference

Alternatively, herbicide-resistant plants according to the presentinvention can also be produced by using genome editing methods to selectfor plant cells comprising herbicide-resistance mutations and thenregenerating herbicide-resistant plants therefrom. “Genome Editing”refers to a type of genetic engineering in which DNA is inserted,deleted or replaced in the genome of an organism using engineerednucleases. These nucleases are known to the skilled artisan to createsite-specific double-strand breaks at desired locations in the genome.The induced double-strand breaks are repaired through nonhomologousend-joining or homologous recombination, resulting in targetedmutations. Known in the art are currently four families of engineerednucleases which can be used for the purposes of the present invention:meganucleases, zinc finger nucleases (ZFNs), transcriptionactivator-like effector-based nucleases (TALEN), and the CRISPR-Cassystem.-For references, see, for example, Esvelt, K M. and Wang, H H.(2013) “Genome-scale engineering for systems and synthetic biology”, MolSyst Biol. 9 (1): 641; Tan, W S. et al., (2012) “Precision editing oflarge animal genomes” Adv Genet. 80: 37-97; Puchta, H. and Fauser, F.(2013) “Gene targeting in plants: 25 years later”, Int. J. Dev. Biol. 57629-637 Boglioli, Elsy and Richard, Magali “Rewriting the book of life:a new era in precision genome editing”, Boston Consulting Group,Retrieved Nov. 30, 2015; Method of the Year 2011. Nat Meth 9 (1), 1-1.

Consequently, in another embodiment, the invention refers to anon-transgenic plant, comprising a plant cell according to the presentinvention, wherein expression of the nucleic acid encoding a mutated PPOin the plant results in the plant's increased resistance touracilpyridine herbicide as compared to a wild type variety of theplant.

In addition to the definition above, the term “plant” is intended toencompass crop plants at any stage of maturity or development, as wellas any tissues or organs (plant parts) taken or derived from any suchplant unless otherwise clearly indicated by context. Plant partsinclude, but are not limited to, stems, roots, flowers, ovules, stamens,leaves, embryos, meristematic regions, callus tissue, anther cultures,gametophytes, sporophytes, pollen, microspores, protoplasts, and thelike.

The plant of the present invention comprises at least one mutated PPOnucleic acid or over-expressed wild-type PPO nucleic acid, and hasincreased tolerance to a uracilpyridine herbicide as compared to awild-type variety of the plant. It is possible for the plants of thepresent invention to have multiple wild-type or mutated PPO nucleicacids from different genomes since these plants can contain more thanone genome. For example, a plant contains two genomes, usually referredto as the A and B genomes. Because PPO is a required metabolic enzyme,it is assumed that each genome has at least one gene coding for the PPOenzyme (i.e. at least one PPO gene). As used herein, the term “PPO genelocus” refers to the position of an PPO gene on a genome, and the terms“PPO gene” and “PPO nucleic acid” refer to a nucleic acid encoding thePPO enzyme. The PPO nucleic acid on each genome differs in itsnucleotide sequence from an PPO nucleic acid on another genome. One ofskill in the art can determine the genome of origin of each PPO nucleicacid through genetic crossing and/or either sequencing methods orexonuclease digestion methods known to those of skill in the art.

The present invention includes plants comprising one, two, three, ormore mutated PPO alleles, wherein the plant has increased tolerance to auracilpyridine herbicide as compared to a wild-type variety of theplant. The mutated PPO alleles can comprise a nucleotide sequenceselected from the group consisting of a polynucleotide encoding apolypeptide as defined in SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29,30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47,48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65,66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83,84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100,101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114,115, 116, 117, 577, 579, 581, 583, 585, 587, 589, 591, 593, 595, 597,599, 601, 603, 605, 607, 609, 611, 613, 615, 617, 619, 621, 623, 625,627, or 637, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276,277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290,291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304,305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318,319, 320, 321, 322, 323, 324, 325, 326, 327328, 329, 330, 331, 332, 333,334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347,348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361,362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375,376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389,390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403,404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417,418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431,432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445,446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459,460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473,474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487,488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501,502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515,516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529,530, 531, 532, 533, 534, 535, 536, 537, 538, 539, 540, 541, 542, 543,544, 545, 546, 547, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557,558, 559, 560, 561, 562, 563, 564, 565,or a variant or derivative,homologue, orthologue, paralogue thereof, a polynucleotide comprising atleast 60 consecutive nucleotides of any of the aforementionedpolynucleotides; and a polynucleotide complementary to any of theaforementioned polynucleotides.

In a particularly preferred embodiment, the mutagenized plant refers toa rice plant of the species Oryza sativa which comprises a mutated PPOallele which comprises a polynucleotide encoding a polypeptide asdefined in SEQ ID NO: 628, 629, 630, 631, 632, 633, 634, 635, or 636.

Preferably, the polynucleotide comprises a nucleic acid sequence asdefined in SEQ ID NO: 638, 639, 640, 641, 642, 643, 644, 645, 646, 647,648,or 649.

Said mutated rice lines were deposited under the terms of the BudapestTreaty on Nov. 8, 2017, and have been assigned the NCIMB accessionnumbers 42873, 42876, 42878, 42871, 42874, 42875, 42870, 42877,and42872.

“Alleles” or “allelic variants” are alternative forms of a given gene,located at the same chromosomal position. Allelic variants encompassSingle Nucleotide Polymorphisms (SNPs), as well as SmallInsertion/Deletion Polymorphisms (INDELs). The size of INDELs is usuallyless than 100 bp. SNPs and INDELs form the largest set of sequencevariants in naturally occurring polymorphic strains of most organisms

The term “variety” refers to a group of plants within a species definedby the sharing of a common set of characteristics or traits accepted bythose skilled in the art as sufficient to distinguish one cultivar orvariety from another cultivar or variety. There is no implication ineither term that all plants of any given cultivar or variety will begenetically identical at either the whole gene or molecular level orthat any given plant will be homozygous at all loci. A cultivar orvariety is considered “true breeding” for a particular trait if, whenthe true-breeding cultivar or variety is self-pollinated, all of theprogeny contain the trait. The terms “breeding line” or “line” refer toa group of plants within a cultivar defined by the sharing of a commonset of characteristics or traits accepted by those skilled in the art assufficient to distinguish one breeding line or line from anotherbreeding line or line. There is no implication in either term that allplants of any given breeding line or line will be genetically identicalat either the whole gene or molecular level or that any given plant willbe homozygous at all loci. A breeding line or line is considered “truebreeding” for a particular trait if, when the true-breeding line orbreeding line is self-pollinated, all of the progeny contain the trait.In the present invention, the trait arises from a mutation in a PPO geneof the plant or seed.

In some embodiments, traditional plant breeding is employed whereby theuracilpyridine herbicides-tolerant trait is introduced in the progenyplant resulting therefrom. In one embodiment, the present inventionprovides a method for producing a uracilpyridine herbicides-tolerantprogeny plant, the method comprising: crossing a parent plant with auracilpyridine herbicides-tolerant plant to introduce the uracilpyridineherbicides-tolerance characteristics of the uracilpyridineherbicides-tolerant plant into the germplasm of the progeny plant,wherein the progeny plant has increased tolerance to the uracilpyridineherbicides relative to the parent plant. In other embodiments, themethod further comprises the step of introgressing the uracilpyridineherbicides-tolerance characteristics through traditional plant breedingtechniques to obtain a descendent plant having the uracilpyridineherbicides-tolerance characteristics.

The herbicide-resistant plants of the invention that comprisepolynucleotides encoding mutated PPO polypeptides also find use inmethods for increasing the herbicide-resistance of a plant throughconventional plant breeding involving sexual reproduction. The methodscomprise crossing a first plant that is a herbicide-resistant plant ofthe invention to a second plant that may or may not be resistant to thesame herbicide or herbicides as the first plant or may be resistant todifferent herbicide or herbicides than the first plant. The second plantcan be any plant that is capable of producing viable progeny plants(i.e., seeds) when crossed with the first plant. Typically, but notnecessarily, the first and second plants are of the same species. Themethods can optionally involve selecting for progeny plants thatcomprise the mutated PPO polypeptides of the first plant and theherbicide resistance characteristics of the second plant. The progenyplants produced by this method of the present invention have increasedresistance to a herbicide when compared to either the first or secondplant or both. When the first and second plants are resistant todifferent herbicides, the progeny plants will have the combinedherbicide tolerance characteristics of the first and second plants. Themethods of the invention can further involve one or more generations ofbackcrossing the progeny plants of the first cross to a plant of thesame line or genotype as either the first or second plant.Alternatively, the progeny of the first cross or any subsequent crosscan be crossed to a third plant that is of a different line or genotypethan either the first or second plant. The present invention alsoprovides plants, plant organs, plant tissues, plant cells, seeds, andnon-human host cells that are transformed with the at least onepolynucleotide molecule, expression cassette, or transformation vectorof the invention. Such transformed plants, plant organs, plant tissues,plant cells, seeds, and non-human host cells have enhanced tolerance orresistance to at least one herbicide, at levels of the herbicide thatkill or inhibit the growth of an untransformed plant, plant tissue,plant cell, or non-human host cell, respectively. Preferably, thetransformed plants, plant tissues, plant cells, and seeds of theinvention are Arabidopsis thaliana and crop plants.

In other aspects, plants of the invention include those plants which, inaddition to being tolerant to uracilpyridine herbicides, have beensubjected to further genetic modifications by breeding, mutagenesis orgenetic engineering, e.g. have been rendered tolerant to applications ofspecific other classes of herbicides, such as AHAS inhibitors; auxinicherbicides; bleaching herbicides such as hydroxyphenylpyruvatedioxygenase (HPPD) inhibitors or phytoene desaturase (PDS) inhibitors;EPSPS inhibitors such as glyphosate; glutamine synthetase (GS)inhibitors such as glufosinate; lipid biosynthesis inhibitors such asacetyl CoA carboxylase (ACCase) inhibitors; or oxynil {i.e. bromoxynilor ioxynil) herbicides as a result of conventional methods of breedingor genetic engineering, Thus, uracilpyridine herbicides-tolerant plantsof the invention can be made resistant to multiple classes of herbicidesthrough multiple genetic modifications, such as resistance to bothglyphosate and glufosinate or to both glyphosate and a herbicide fromanother class such as HPPD inhibitors, AHAS inhibitors, or ACCaseinhibitors. These herbicide resistance technologies are, for example,described in Pest Management Science (at volume, year, page):61, 2005,246; 61, 2005, 258; 61, 2005, 277; 61, 2005, 269; 61, 2005, 286; 64,2008, 326; 64, 2008, 332; Weed Science 57, 2009, 108; Australian Journalof Agricultural Research 58, 2007, 708; Science 316, 2007, 1185; andreferences quoted therein. For example, uracilpyridineherbicides-tolerant plants of the invention, in some embodiments, may betolerant to ACCase inhibitors, such as “dims” {e.g., cycloxydim,sethoxydim, clethodim, or tepraloxydim), “fops” {e.g., clodinafop,diclofop, fluazifop, haloxyfop, or quizalofop), and “dens” (such aspinoxaden); to auxinic herbicides, such as dicamba; to EPSPS inhibitors,such as glyphosate; to other PPO inhibitors; and to GS inhibitors, suchas glufosinate.

In addition to these classes of inhibitors, uracilpyridineherbicides-tolerant plants of the invention may also be tolerant toherbicides having other modes of action, for example,chlorophyll/carotenoid pigment inhibitors, cell membrane disrupters,photosynthesis inhibitors, cell division inhibitors, root inhibitors,shoot inhibitors, and combinations thereof.

Such tolerance traits may be expressed, e.g.: as mutant or wildtype PPOproteins, as mutant AHASL proteins, mutant ACCase proteins, mutant EPSPSproteins, or mutant glutamine synthetase proteins; or as mutant native,inbred, or transgenic aryloxyalkanoate dioxygenase (AAD or DHT),haloarylnitrilase (BXN), 2,2-dichloropropionic acid dehalogenase (DEH),glyphosate-N-acetyltransferase (GAT), glyphosate decarboxylase (GDC),glyphosate oxidoreductase (GOX), glutathione-S-transferase (GST),phosphinothricin acetyltransferase (PAT or bar), or CYP450s proteinshaving an herbicide-degrading activity.

uracilpyridine herbicides-tolerant plants hereof can also be stackedwith other traits including, but not limited to, pesticidal traits suchas Bt Cry and other proteins having pesticidal activity towardcoleopteran, lepidopteran, nematode, or other pests; nutrition ornutraceutical traits such as modified oil content or oil profile traits,high protein or high amino acid concentration traits, and other traittypes known in the art.

Furthermore, in other embodiments, uracilpyridine herbicides-tolerantplants are also covered which are, by the use of recombinant DNAtechniques and/or by breeding and/or otherwise selected for suchcharacteristics, rendered able to synthesize one or more insecticidalproteins, especially those known from the bacterial genus Bacillus,particularly from Bacillus thuringiensis, such as [delta]-endotoxins,e.g. CryIA(b), CryIA(c), CryIF, CryIF(a2), CryIIA(b), CryIIIA,CryIIIB(b1) or Cry9c; vegetative insecticidal proteins (VIP), e.g. VIP1,VIP2, VIP3 or VIP3A; insecticidal proteins of bacteria colonizingnematodes, e.g. Photorhabdus spp. or Xenorhabdus spp.; toxins producedby animals, such as scorpion toxins, arachnid toxins, wasp toxins, orother insect-specific neurotoxins; toxins produced by fungi, suchstreptomycete toxins; plant lectins, such as pea or barley lectins;agglutinins; proteinase inhibitors, such as trypsin inhibitors, serineprotease inhibitors, patatin, cystatin or papain inhibitors;ribosome-inactivating proteins (RIP), such as ricin, maize-RIP, abrin,luffin, saporin or bryodin; steroid metabolism enzymes, such as3-hydroxy-steroid oxidase, ecdysteroid-IDP-glycosyl-transferase,cholesterol oxidases, ecdysone inhibitors or HMG-CoA-reductase; ionchannel blockers, such as blockers of sodium or calcium channels;juvenile hormone esterase; diuretic hormone receptors (helicokininreceptors); stilben synthase, bibenzyl synthase, chitinases orglucanases. In the context of the present invention these insecticidalproteins or toxins are to be understood expressly also as pre-toxins,hybrid proteins, truncated or otherwise modified proteins. Hybridproteins are characterized by a new combination of protein domains,(see, e.g. WO 02/015701). Further examples of such toxins or geneticallymodified plants capable of synthesizing such toxins are disclosed, e.g.,in EP-A 374 753, WO 93/007278, WO 95/34656, EP-A 427 529, EP-A 451 878,WO 03/18810 und WO 03/52073. The methods for producing such geneticallymodified plants are generally known to the person skilled in the art andare described, e.g. in the publications mentioned above. Theseinsecticidal proteins contained in the genetically modified plantsimpart to the plants producing these proteins tolerance to harmful pestsfrom all taxonomic groups of arthropods, especially to beetles(Coeloptera), two-winged insects (Diptera), and moths (Lepidoptera) andto nematodes (Nematoda).

In some embodiments, expression of one or more protein toxins (e.g.,insecticidal proteins) in the uracilpyridine herbicides-tolerant plantsis effective for controlling organisms that include, for example,members of the classes and orders: Coleoptera such as the American beanweevil Acanthoscelides obtectus; the leaf beetle Agelastica alni; clickbeetles (Agriotes lineatus, Agriotes obscurus, Agriotes bicolor); thegrain beetle Ahasverus advena; the summer schafer Amphimallonsolstitialis; the furniture beetle Anobium punctatum; Anthonomus spp.(weevils); the Pygmy mangold beetle Atomaria linearis; carpet beetles(Anthrenus spp., Attagenus spp.); the cowpea weevil Callosobruchusmaculates; the fried fruit beetle Carpophilus hemipterus; the cabbageseedpod weevil Ceutorhynchus assimilis; the rape winter stem weevilCeutorhynchus picitarsis; the wireworms Conoderus vespertinus andConoderus falli; the banana weevil Cosmopolites sordidus; the NewZealand grass grub Costelytra zealandica; the June beetle Cotinisnitida; the sunflower stem weevil Cylindrocopturus adspersus; the larderbeetle Dermestes lardarius; the corn rootworms Diabrotica virgifera,Diabrotica virgifera virgifera, and Diabrotica barberi; the Mexican beanbeetle Epilachna varivestis; the old house borer Hylotropes bajulus; thelucerne weevil Hypera postica; the shiny spider beetle Gibbiumpsylloides; the cigarette beetle Lasioderma serricorne; the Coloradopotato beetle Leptinotarsa decemlineata; Lyctus beetles {Lyctus spp.,the pollen beetle Meligethes aeneus; the common cockshafer Melolonthamelolontha; the American spider beetle Mezium americanum; the goldenspider beetle Niptus hololeuc s; the grain beetles Oryzaephilussurinamensis and Oryzaephilus Mercator; the black vine weevilOtiorhynchus sulcatus; the mustard beetle Phaedon cochleariae, thecrucifer flea beetle Phyllotreta cruciferae; the striped flea beetlePhyllotreta striolata; the cabbage steam flea beetle Psylliodeschrysocephala; Ptinus spp. (spider beetles); the lesser grain borerRhizopertha dominica; the pea and been weevil Sitona lineatus; the riceand granary beetles Sitophilus oryzae and Sitophilus granaries; the redsunflower seed weevil Smicronyx fulvus; the drugstore beetle Stegobiumpaniceum; the yellow mealworm beetle Tenebrio molitor, the flour beetlesTribolium castaneum and Tribolium confusum; warehouse and cabinetbeetles {Trogoderma spp.); the sunflower beetle Zygogrammaexclamationis; Dermaptera (earwigs) such as the European earwigForficula auricularia and the striped earwig Labidura riparia;Dictyoptera such as the oriental cockroach Blatta orientalis; thegreenhouse millipede Oxidus gracilis; the beet fly Pegomyia betae; thefrit fly Oscinella frit; fruitflies (Dacus spp., Drosophila spp.);Isoptera (termites) including species from the familes Hodotermitidae,Kalotermitidae, Mastotermitidae, Rhinotermitidae, Serritermitidae,Termitidae, Termopsidae; the tarnished plant bug Lygus lineolaris; theblack bean aphid Aphis fabae; the cotton or melon aphid Aphis gossypii;the green apple aphid Aphis pomi; the citrus spiny whiteflyAleurocanthus spiniferus; the sweet potato whitefly Bemesia tabaci; thecabbage aphid Brevicoryne brassicae; the pear psylla Cacopsyllapyricola; the currant aphid Cryptomyzus ribis; the grape phylloxeraDaktulosphaira vitifoliae; the citrus psylla Diaphorina citri; thepotato leafhopper Empoasca fabae; the bean leafhopper Empoasca Solana;the vine leafhopper Empoasca vitis; the woolly aphid Eriosoma lanigerum;the European fruit scale Eulecanium corni; the mealy plum aphidHyalopterus arundinis; the small brown planthopper Laodelphaxstriatellus; the potato aphid Macrosiphum euphorbiae; the green peachaphid Myzus persicae; the green rice leafhopper Nephotettix cinticeps;the brown planthopper Nilaparvata lugens; the hop aphid Phorodon humuli;the bird-cherry aphid Rhopalosiphum padi; the grain aphid Sitobionavenae; Lepidoptera such as Adoxophyes orana (summer fruit tortrixmoth); Archips podana (fruit tree tortrix moth); Bucculatrix pyrivorella(pear leafminer); Bucculatrix thurberiella (cotton leaf perforator);Bupalus piniarius (pine looper); Carpocapsa pomonella (codling moth);Chilo suppressalis (striped rice borer); Choristoneura fumiferana(eastern spruce budworm); Cochylis hospes (banded sunflower moth);Diatraea grandiosella (southwestern corn borer); Eupoecilia ambiguella(European grape berry moth); Helicoverpa armigera (cotton bollworm);Helicoverpa zea (cotton bollworm); Heliothis vires cens (tobaccobudworm), Homeosoma electellum (sunflower moth); Homona magnanima(oriental tea tree tortrix moth); Lithocolletis blancardella (spottedtentiform leafminer); Lymantria dispar (gypsy moth); Malacosoma neustria(tent caterpillar); Mamestra brassicae (cabbage armyworm); Mamestraconfigurata (Bertha armyworm); Operophtera brumata (winter moth);Ostrinia nubilalis (European corn borer), Panolis flammea (pine beautymoth), Phyllocnistis citrella (citrus leafminer); Pieris brassicae(cabbage white butterfly); Rachiplusia ni (soybean looper); Spodopteraexigua (beet armyworm); Spodoptera littoralis (cotton leafworm); Syleptaderogata (cotton leaf roller); Trichoplusia ni (cabbage looper);Orthoptera such as the common cricket Acheta domesticus, tree locusts(Anacridium spp.), the migratory locust Locusta migratoria, thetwostriped grasshopper Melanoplus bivittatus, the differentialgrasshopper Melanoplus differ entialis, the redlegged grasshopperMelanoplus femurrubrum, the migratory grasshopper Melanoplussanguinipes, the northern mole cricket Neocurtilla hexadectyla, the redlocust Nomadacris septemfasciata, the shortwinged mole cricketScapteriscus abbreviatus, the southern mole cricket Scapteriscusborellii, the tawny mole cricket Scapteriscus vicinus, and the desertlocust Schistocerca gregaria; Symphyla such as the garden symphylanScutigerella immaculata; Thysanoptera such as the tobacco thripsFrankliniella fusca, the flower thrips Frankliniella intonsa, thewestern flower thrips Frankliniella occidentalism the cotton bud thripsFrankliniella schultzei, the banded greenhouse thrips Hercinothripsfemoralis, the soybean thrips Neohydatothrips variabilis, Kelly's citrusthrips Pezothrips kellyanus, the avocado thrips Scirtothrips perseae,the melon thrips Thrips palmi, and the onion thrips Thrips tabaci; andthe like, and combinations comprising one or more of the foregoingorganisms.

In some embodiments, expression of one or more protein toxins (e.g.,insecticidal proteins) in the uracilpyridine herbicides-tolerant plantsis effective for controlling flea beetles, i.e. members of the fleabeetle tribe of family Chrysomelidae, preferably against Phyllotretaspp., such as Phyllotreta cruciferae and/or Phyllotreta triolata. Inother embodiments, expression of one or more protein toxins {e.g.,insecticidal proteins) in the uracilpyridine herbicides-tolerant plantsis effective for controlling cabbage seedpod weevil, the Berthaarmyworm, Lygus bugs, or the diamondback moth.

Furthermore, in one embodiment, uracilpyridine herbicides-tolerantplants are also covered which are, e.g. by the use of recombinant DNAtechniques and/or by breeding and/or otherwise selected for such traits,rendered able to synthesize one or more proteins to increase theresistance or tolerance of those plants to bacterial, viral or fungalpathogens. The methods for producing such genetically modified plantsare generally known to the person skilled in the art.

Furthermore, in another embodiment, uracilpyridine herbicides-tolerantplants are also covered which are, e.g. by the use of recombinant DNAtechniques and/or by breeding and/or otherwise selected for such traits,rendered able to synthesize one or more proteins to increase theproductivity (e.g. oil content), tolerance to drought, salinity or othergrowth-limiting environmental factors or tolerance to pests and fungal,bacterial or viral pathogens of those plants.

Furthermore, in other embodiments, uracilpyridine herbicides-tolerantplants are also covered which are, e.g. by the use of recombinant DNAtechniques and/or by breeding and/or otherwise selected for such traits,altered to contain a modified amount of one or more substances or newsubstances, for example, to improve human or animal nutrition, e.g. oilcrops that produce health-promoting long-chain omega-3 fatty acids orunsaturated omega-9 fatty acids (e.g. Nexera® rape, Dow Agro Sciences,Canada).

Furthermore, in some embodiments, uracilpyridine herbicides-tolerantplants are also covered which are, e.g. by the use of recombinant DNAtechniques and/or by breeding and/or otherwise selected for such traits,altered to contain increased amounts of vitamins and/or minerals, and/orimproved profiles of nutraceutical compounds.

In one embodiment, uracilpyridine herbicides-tolerant plants of thepresent invention, relative to a wild-type plant, comprise an increasedamount of, or an improved profile of, a compound selected from the groupconsisting of: glucosinolates (e.g., glucoraphanin(4-methylsulfinylbutyl-glucosinolate), sulforaphane,3-indolylmethyl-glucosinolate(glucobrassicin),I-methoxy-3-indolylmethyl-glucosinolate (neoglucobrassicin)); phenolics(e.g., flavonoids (e.g., quercetin, kaempferol), hydroxycinnamoylderivatives (e.g., 1,2,2′-trisinapoylgentiobiose,1,2-diferuloylgentiobiose, I,2′-disinapoyl-2-feruloylgentiobiose,3-0-caffeoyl-quinic (neochlorogenic acid)); and vitamins and minerals(e.g., vitamin C, vitamin E, carotene, folic acid, niacin, riboflavin,thiamine, calcium, iron, magnesium, potassium, selenium, and zinc).

In another embodiment, uracilpyridine herbicides-tolerant plants of thepresent invention, relative to a wild-type plant, comprise an increasedamount of, or an improved profile of, a compound selected from the groupconsisting of: progoitrin; isothiocyanates; indoles (products ofglucosinolate hydrolysis); glutathione; carotenoids such asbeta-carotene, lycopene, and the xanthophyll carotenoids such as luteinand zeaxanthin; phenolics comprising the flavonoids such as theflavonols (e.g. quercetin, rutin), the flavans/tannins (such as theprocyanidins comprising coumarin, proanthocyanidins, catechins, andanthocyanins); flavones; phytoestrogens such as coumestans, lignans,resveratrol, isoflavones e.g. genistein, daidzein, and glycitein;resorcyclic acid lactones; organosulphur compounds; phytosterols;terpenoids such as carnosol, rosmarinic acid, glycyrrhizin and saponins;chlorophyll; chlorphyllin, sugars, anthocyanins, and vanilla. In otherembodiments, uracilpyridine herbicides-tolerant plants of the presentinvention, relative to a wild-type plant, comprise an increased amountof, or an improved profile of, a compound selected from the groupconsisting of: vincristine, vinblastine, taxanes (e.g., taxol(paclitaxel), baccatin III, 10-desacetylbaccatin III, 10-desacetyltaxol, xylosyl taxol, 7-epitaxol, 7-epibaccatin III,10-desacetylcephalomannine, 7-epicephalomannine, taxotere,cephalomannine, xylosyl cephalomannine, taxagifine, 8-benxoyloxytaxagifine, 9-acetyloxy taxusin, 9-hydroxy taxusin, taiwanxam, taxaneIa, taxane Ib, taxane Ic, taxane Id, GMP paclitaxel, 9-dihydro13-acetylbaccatin III, 10-desacetyl-7-epitaxol, tetrahydrocannabinol(THC), cannabidiol (CBD), genistein, diadzein, codeine, morphine,quinine, shikonin, ajmalacine, serpentine, and the like.

It is to be understood that the plant of the present invention cancomprise a wild type PPO nucleic acid in addition to a mutated PPOnucleic acid. It is contemplated that the uracilpyridine herbicidetolerant lines may contain a mutation in only one of multiple PPOisoenzymes. Therefore, the present invention includes a plant comprisingone or more mutated PPO nucleic acids in addition to one or more wildtype PPO nucleic acids.

In another embodiment, the invention refers to a seed produced by atransgenic plant comprising a plant cell of the present invention,wherein the seed is true breeding for an increased resistance to auracilpyridine herbicide as compared to a wild type variety of the seed.

In another embodiment, the invention refers to a method of producing atransgenic plant cell with an increased resistance to a uracilpyridineherbicide as compared to a wild type variety of the plant cellcomprising, transforming the plant cell with an expression cassettecomprising a mutated PPO nucleic acid.

In another embodiment, the invention refers to a method of producing atransgenic plant comprising, (a) transforming a plant cell with anexpression cassette comprising a mutated PPO nucleic acid, and (b)generating a plant with an increased resistance to uracilpyridineherbicide from the plant cell.

Consequently, mutated PPO nucleic acids of the invention are provided inexpression cassettes for expression in the plant of interest. Thecassette will include regulatory sequences operably linked to a mutatedPPO nucleic acid sequence of the invention. The term “regulatoryelement” as used herein refers to a polynucleotide that is capable ofregulating the transcription of an operably linked polynucleotide. Itincludes, but not limited to, promoters, enhancers, introns, 5′ UTRs,and 3′ UTRs. By “operably linked” is intended a functional linkagebetween a promoter and a second sequence, wherein the promoter sequenceinitiates and mediates transcription of the DNA sequence correspondingto the second sequence. Generally, operably linked means that thenucleic acid sequences being linked are contiguous and, where necessaryto join two protein coding regions, contiguous and in the same readingframe. The cassette may additionally contain at least one additionalgene to be cotransformed into the organism. Alternatively, theadditional gene(s) can be provided on multiple expression cassettes.

In a preferred embodiment, the expression cassette comprises thesequence of SEQ ID NO:240, 241, 242, 243, 244, 245, 246, 247, 248, 249,250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, or 264.

Such an expression cassette is provided with a plurality of restrictionsites for insertion of the mutated PPO nucleic acid sequence to be underthe transcriptional regulation of the regulatory regions. The expressioncassette may additionally contain selectable marker genes.

The expression cassette of the present invention will include in the5′-3′ direction of transcription, a transcriptional and translationalinitiation region (i.e., a promoter), a mutated PPO encoding nucleicacid sequence of the invention, and a transcriptional and translationaltermination region (i.e., termination region) functional in plants. Thepromoter may be native or analogous, or foreign or heterologous, to theplant host and/or to the mutated PPO nucleic acid sequence of theinvention. Additionally, the promoter may be the natural sequence oralternatively a synthetic sequence. Where the promoter is “foreign” or“heterologous” to the plant host, it is intended that the promoter isnot found in the native plant into which the promoter is introduced.Where the promoter is “foreign” or “heterologous” to the mutated PPOnucleic acid sequence of the invention, it is intended that the promoteris not the native or naturally occurring promoter for the operablylinked mutated PPO nucleic acid sequence of the invention. As usedherein, a chimeric gene comprises a coding sequence operably linked to atranscription initiation region that is heterologous to the codingsequence.

While it may be preferable to express the mutated PPO nucleic acids ofthe invention using heterologous promoters, the native promotersequences may be used. Such constructs would change expression levels ofthe mutated PPO protein in the plant or plant cell. Thus, the phenotypeof the plant or plant cell is altered.

The termination region may be native with the transcriptional initiationregion, may be native with the operably linked mutated PPO sequence ofinterest, may be native with the plant host, or may be derived fromanother source (i.e., foreign or heterologous to the promoter, themutated PPO nucleic acid sequence of interest, the plant host, or anycombination thereof). Convenient termination regions are available fromthe Ti-plasmid of A. tumefaciens, such as the octopine synthase andnopaline synthase termination regions. See also Guerineau et al. (1991)Mol. Gen. Genet. 262: 141-144; Proudfoot (1991) Cell 64:671-674;Sanfacon et al. (1991) Genes Dev. 5: 141-149; Mogen et al. (1990) PlantCell 2: 1261-1272; Munroe et al. (1990) Gene 91: 151-158; Ballas t al.(1989) Nucleic Acids Res. 17:7891-7903; and Joshi et al. (1987) NucleicAcid Res. 15:9627-9639. Where appropriate, the gene(s) may be optimizedfor increased expression in the transformed plant. That is, the genescan be synthesized using plant-preferred codons for improved expression.See, for example, Campbell and Gowri (1990) Plant Physiol. 92: 1-11 fora discussion of host-preferred codon usage. Methods are available in theart for synthesizing plant-preferred genes. See, for example, U.S. Pat.Nos. 5,380,831, and 5,436,391, and Murray et al. (1989) Nucleic AcidsRes. 17:477-498, herein incorporated by reference.

Additional sequence modifications are known to enhance gene expressionin a cellular host. These include elimination of sequences encodingspurious polyadenylation signals, exon-intron splice site signals,transposon-like repeats, and other such well-characterized sequencesthat may be deleterious to gene expression. The G-C content of thesequence may be adjusted to levels average for a given cellular host, ascalculated by reference to known genes expressed in the host cell. Whenpossible, the sequence is modified to avoid predicted hairpin secondarymRNA structures. Nucleotide sequences for enhancing gene expression canalso be used in the plant expression vectors. These include the intronsof the maize Adhl, intronl gene (Callis et al. Genes and Development 1:1183-1200, 1987), and leader sequences, (W-sequence) from the TobaccoMosaic virus (TMV), Maize Chlorotic Mottle Virus and Alfalfa MosaicVirus (Gallie et al. Nucleic Acid Res. 15:8693-8711, 1987 and Skuzeskiet al. Plant Mol. Biol. 15:65-79, 1990). The first intron from theshrunken-1 locus of maize, has been shown to increase expression ofgenes in chimeric gene constructs. U.S. Pat. Nos. 5,424,412 and5,593,874 disclose the use of specific introns in gene expressionconstructs, and Gallie et al. (Plant Physiol. 106:929-939, 1994) alsohave shown that introns are useful for regulating gene expression on atissue specific basis. To further enhance or to optimize mutated PPOgene expression, the plant expression vectors of the invention may alsocontain DNA sequences containing matrix attachment regions (MARs). Plantcells transformed with such modified expression systems, then, mayexhibit overexpression or constitutive expression of a nucleotidesequence of the invention.

The expression cassettes of the present invention may additionallycontain 5′ leader sequences in the expression cassette construct. Suchleader sequences can act to enhance translation. Translation leaders areknown in the art and include: picornavirus leaders, for example, EMCVleader (Encephalomyocarditis 5′ noncoding region) (Elroy-Stein et al.(1989) Proc. Natl. Acad. ScL USA 86:6126-6130); potyvirus leaders, forexample, TEV leader (Tobacco Etch Virus) (Gallie et al. (1995) Gene165(2):233-238), MDMV leader (Maize Dwarf Mosaic Virus) (Virology154:9-20), and human immunoglobulin heavy-chain binding protein (BiP)(Macejak et al. (1991) Nature 353:90-94); untranslated leader from thecoat protein mRNA of alfalfa mosaic virus (AMV RNA 4) (Jobling et al.(1987) Nature 325:622-625); tobacco mosaic virus leader (TMV) (Gallie etal. (1989) in Molecular Biology of RNA, ed. Cech (Liss, New York), pp.237-256); and maize chlorotic mottle virus leader (MCMV) (Lommel et al.(1991) Virology 81:382-385). See also, Della-Cioppa et al. (1987) PlantPhysiol. 84:965-968. Other methods known to enhance translation can alsobe utilized, for example, introns, and the like.

In preparing the expression cassette, the various DNA fragments may bemanipulated, so as to provide for the DNA sequences in the properorientation and, as appropriate, in the proper reading frame. Towardthis end, adapters or linkers may be employed to join the DNA fragmentsor other manipulations may be involved to provide for convenientrestriction sites, removal of superfluous DNA, removal of restrictionsites, or the like. For this purpose, in vitro mutagenesis, primerrepair, restriction, annealing, resubstitutions, e.g., transitions andtrans versions, may be involved.

A number of promoters can be used in the practice of the invention. Thepromoters can be selected based on the desired outcome. The nucleicacids can be combined with constitutive, tissue-preferred, or otherpromoters for expression in plants. Such constitutive promoters include,for example, the core promoter of the Rsyn7 promoter and otherconstitutive promoters disclosed in WO 99/43838 and U.S. Pat. No.6,072,050; the core CaMV 35S promoter (Odell et al. (1985) Nature313:810-812); rice actin (McElroy et al. (1990) Plant Cell 2: 163-171);ubiquitin (Christensen et al. (1989) Plant Mol. Biol. 12:619-632 andChristensen et al. (1992) Plant Mol. Biol. 18:675-689); pEMU (Last etal. (1991) Theor. Appl. Genet. 81:581-588); MAS (Velten et al. (1984)EMBO J. 3:2723-2730); ALS promoter (U.S. Pat. No. 5,659,026), and thelike. Other constitutive promoters include, for example, U.S. Pat. Nos.5,608,149; 5,608,144; 5,604,121; 5,569,597; 5,466,785; 5,399,680;5,268,463; 5,608,142; and 6,177,611.

Tissue-preferred promoters can be utilized to target enhanced mutatedPPO expression within a particular plant tissue. Such tissue-preferredpromoters include, but are not limited to, leaf-preferred promoters,root-preferred promoters, seed-preferred promoters, and stem-preferredpromoters. Tissue-preferred promoters include Yamamoto et al. (1997)Plant J. 12(2):255-265; Kawamata et al. (1997) Plant Cell Physiol.38(7):792-803; Hansen et al. (1997) Mol. Gen Genet. 254(3):337-343;Russell et al. (1997) Transgenic Res. 6(2): 157-168; Rinehart et al.(1996) Plant Physiol. 112(3): 1331-1341; Van Camp et al. (1996) PlantPhysiol. 112(2):525-535; Canevascini et al. (1996) Plant Physiol.112(2):513-524; Yamamoto et al. (1994) Plant Cell Physiol.35(5):773-778; Lam (1994) Results Probl. Cell Differ. 20: 181-196;Orozco et al. (1993) Plant Mol Biol. 23(6): 1129-1138; Matsuokae/[alpha]/. (1993) Proc Natl. Acad. Sci. USA 90(20):9586-9590; andGuevara-Garcia et al. (1993) Plant J. 4(3):495-505. Such promoters canbe modified, if necessary, for weak expression. In one embodiment, thenucleic acids of interest are targeted to the chloroplast forexpression. In this manner, where the nucleic acid of interest is notdirectly inserted into the chloroplast, the expression cassette willadditionally contain a chloroplast-targeting sequence comprising anucleotide sequence that encodes a chloroplast transit peptide to directthe gene product of interest to the chloroplasts. Such transit peptidesare known in the art. With respect to chloroplast-targeting sequences,“operably linked” means that the nucleic acid sequence encoding atransit peptide (i.e., the chloroplast-targeting sequence) is linked tothe mutated PPO nucleic acid of the invention such that the twosequences are contiguous and in the same reading frame. See, forexample, Von Heijne et al. (1991) Plant Mol. Biol. Rep. 9: 104-126;Clark et al. (1989) J. Biol. Chem. 264:17544-17550; Della-Cioppa et al.(1987) Plant Physiol. 84:965-968; Romer et al. (1993) Biochem. Biophys.Res. Commun. 196:1414-1421; and Shah et al. (1986) Science 233:478-481.While the mutated PPO proteins of the invention include a nativechloroplast transit peptide, any chloroplast transit peptide known inthe art can be fused to the amino acid sequence of a mature mutated PPOprotein of the invention by operably linking a choloroplast-targetingsequence to the 5′-end of a nucleotide sequence encoding a maturemutated PPO protein of the invention. Chloroplast targeting sequencesare known in the art and include the chloroplast small subunit ofribulose-1,5-bisphosphate carboxylase (Rubisco) (de Castro Silva Filhoet al. (1996) Plant Mol. Biol. 30:769-780; Schnell et al. (1991) J.Biol. Chem. 266(5):3335-3342); 5-(enolpyruvyl)shikimate-3-phosphatesynthase (EPSPS) (Archer et al. (1990) J. Bioenerg. Biomemb.22(6):789-810); tryptophan synthase (Zhao et al. (1995) J. Biol. Chem.270(11):6081-6087); plastocyanin(Lawrence et al. (1997) J. Biol. Chem.272(33):20357-20363); chorismate synthase (Schmidt et al. (1993) J.Biol. Chem. 268(36):27447-27457); and the light harvesting chlorophylla/b binding protein (LHBP) (Lamppa et al. (1988) J. Biol. Chem. 263:14996-14999). See also Von Heijne et al. (1991) Plant Mol. Biol. Rep. 9:104-126; Clark et al. (1989) J. Biol. Chem. 264:17544-17550;Della-Cioppa et al. (1987) Plant Physiol. 84:965-968; Romer et al.(1993) Biochem. Biophys. Res. Commun. 196: 1414-1421; and Shah et al.(1986) Science 233:478-481.

In a preferred embodiment, the transit peptide comprises the amino acidsequence of SEQ ID NO: 129, 130, 131, 132, 133, 134, 135, 136, 137, 138,139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152,153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166,167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180,181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194,195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208,209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222,223, 224, 225, 226.

Preferred expression cassettes comprise a transit peptide fromAmaranthus PPO-2 fused to PPO or PPO like polypeptides, such as chimericexpression cassettes having the SEQ ID NO:240, 241, 242, 243, 244, 245,246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259,260, 261, 262,or 264

Methods for transformation of chloroplasts are known in the art. See,for example, Svab et al. (1990) Proc. Natl. Acad. ScL USA 87:8526-8530;Svab and Maliga (1993) Proc. Natl. Acad. Sci. USA 90:913-917; Svab andMaliga (1993) EMBO J. 12:601-606. The method relies on particle gundelivery of DNA containing a selectable marker and targeting of the DNAto the plastid genome through homologous recombination. Additionally,plastid transformation can be accomplished by transactivation of asilent plastid-borne transgene by tissue-preferred expression of anuclear-encoded and plastid-directed RNA polymerase. Such a system hasbeen reported in McBride et al. (1994) Proc. Natl. Acad. Sci. USA91:7301-7305. The nucleic acids of interest to be targeted to thechloroplast may be optimized for expression in the chloroplast toaccount for differences in codon usage between the plant nucleus andthis organelle. In this manner, the nucleic acids of interest may besynthesized using chloroplast-preferred codons. See, for example, U.S.Pat. No. 5,380,831, herein incorporated by reference.

In a preferred embodiment, the mutated PPO nucleic acid comprises apolynucleotide sequence selected from the group consisting of: a) apolynucleotide encoding a polypeptide as shown in SEQ ID NO: 1, 2, 3, 4,5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41,42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59,60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77,78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95,96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110,111, 112, 113, 114, 115, 116, 117, 577, 579, 581, 583, 585, 587, 589,591, 593, 595, 597, 599, 601, 603, 605, 607, 609, 611, 613, 615, 617,619, 621, 623, 625, 627, or 637,or a variant or derivative thereof; b) apolynucleotide comprising at least 60 consecutive nucleotides of any ofa); and c) a polynucleotide complementary to the polynucleotide of anyof a) through b)

Preferably, the expression cassette of the present invention furthercomprises a transcription initiation regulatory region and a translationinitiation regulatory region that are functional in the plant.

While the polynucleotides of the invention find use as selectable markergenes for plant transformation, the expression cassettes of theinvention can include another selectable marker gene for the selectionof transformed cells. Selectable marker genes, including those of thepresent invention, are utilized for the selection of transformed cellsor tissues. Marker genes include, but are not limited to, genes encodingantibiotic resistance, such as those encoding neomycinphosphotransferase II (NEO) and hygromycin phosphotransferase (HPT), aswell as genes conferring resistance to herbicidal compounds, such asglufosinate ammonium, bromoxynil, imidazolinones, and2,4-dichlorophenoxyacetate (2,4-D). See generally, Yarranton (1992)Curr. Opin. Biotech. 3: 506-511; Christophers on et al (1992) Proc.Natl. Acad. ScL USA 89:6314-6318; Yao et al. (1992) Cell 71:63-72;Reznikoff (1992) Mol Microbiol 6:2419-2422; Barkley et al (1980) in TheOperon, pp. 177-220; Hu et al (1987) Cell 48:555-566; Brown et al (1987)Cell 49:603-612; Figge et al (1988) Cell 52:713-722; Deuschle et al(1989) Proc. Natl Acad. AcL USA 86:5400-5404; Fuerst et al (1989) Proc.Natl Acad. ScL USA 86:2549-2553; Deuschle et al (1990) Science248:480-483; Gossen (1993) Ph.D. Thesis, University of Heidelberg;Reines et al (1993) Proc. Natl Acad. ScL USA 90: 1917-1921; Labow et al(1990) Mol Cell Biol 10:3343-3356; Zambretti et al (1992) Proc. NatlAcad. ScL USA 89:3952-3956; Bairn et al (1991) Proc. Natl Acad. ScL USA88:5072-5076; Wyborski et al (1991) Nucleic Acids Res. 19:4647-4653;Hillenand-Wissman (1989) Topics Mol Struc. Biol 10: 143-162; Degenkolbet al (1991) Antimicrob. Agents Chemother. 35: 1591-1595; Kleinschnidtet al (1988) Biochemistry 27: 1094-1104; Bonin (1993) Ph.D. Thesis,University of Heidelberg; Gossen et al (1992) Proc. Natl Acad. ScL USA89:5547-5551; Oliva et al (1992) Antimicrob. Agents Chemother.36:913-919; Hlavka et al (1985) Handbook of Experimental Pharmacology,Vol. 78 (Springer-Verlag, Berlin); Gill et al (1988) Nature 334:721-724.Such disclosures are herein incorporated by reference. The above list ofselectable marker genes is not meant to be limiting. Any selectablemarker gene can be used in the present invention.

The invention further provides an isolated recombinant expression vectorcomprising the expression cassette containing a mutated PPO nucleic acidas described above, wherein expression of the vector in a host cellresults in increased tolerance to a uracilpyridine herbicide as comparedto a wild type variety of the host cell. As used herein, the term“vector” refers to a nucleic acid molecule capable of transportinganother nucleic acid to which it has been linked. One type of vector isa “plasmid,” which refers to a circular double stranded DNA loop intowhich additional DNA segments can be ligated. Another type of vector isa viral vector, wherein additional DNA segments can be ligated into theviral genome. Certain vectors are capable of autonomous replication in ahost cell into which they are introduced (e.g., bacterial vectors havinga bacterial origin of replication and episomal mammalian vectors). Othervectors (e.g., non-episomal mammalian vectors) are integrated into thegenome of a host cell upon introduction into the host cell, and therebyare replicated along with the host genome. Moreover, certain vectors arecapable of directing the expression of genes to which they areoperatively linked. Such vectors are referred to herein as “expressionvectors.” In general, expression vectors of utility in recombinant DNAtechniques are often in the form of plasmids. In the presentspecification, “plasmid” and “vector” can be used interchangeably as theplasmid is the most commonly used form of vector. However, the inventionis intended to include such other forms of expression vectors, such asviral vectors (e.g., replication defective retroviruses, adenoviruses,and adeno-associated viruses), which serve equivalent functions.

The recombinant expression vectors of the invention comprise a nucleicacid of the invention in a form suitable for expression of the nucleicacid in a host cell, which means that the recombinant expression vectorsinclude one or more regulatory sequences, selected on the basis of thehost cells to be used for expression, which is operably linked to thenucleic acid sequence to be expressed. Regulatory sequences includethose that direct constitutive expression of a nucleotide sequence inmany types of host cells and those that direct expression of thenucleotide sequence only in certain host cells or under certainconditions. It will be appreciated by those skilled in the art that thedesign of the expression vector can depend on such factors as the choiceof the host cell to be transformed, the level of expression ofpolypeptide desired, etc. The expression vectors of the invention can beintroduced into host cells to thereby produce polypeptides or peptides,including fusion polypeptides or peptides, encoded by nucleic acids asdescribed herein (e.g., mutated PPO polypeptides, fusion polypeptides,etc.).

In a preferred embodiment of the present invention, the mutated PPOpolypeptides are expressed in plants and plants cells such asunicellular plant cells (such as algae) (See Falciatore et al., 1999,Marine Biotechnology 1(3):239-251 and references therein) and plantcells from higher plants (e.g., the spermatophytes, such as cropplants). A mutated PPO polynucleotide may be “introduced” into a plantcell by any means, including transfection, transformation ortransduction, electroporation, particle bombardment, agroinfection,biolistics, and the like.

Suitable methods for transforming or transfecting host cells includingplant cells can be found in Sambrook et al. (Molecular Cloning: ALaboratory Manual. 2nd, ed., Cold Spring Harbor Laboratory, Cold SpringHarbor Laboratory Press, Cold Spring Harbor, N.Y., 1989) and otherlaboratory manuals such as Methods in Molecular Biology, 1995, Vol. 44,Agrobacterium protocols, ed: Gartland and Davey, Humana Press, Totowa,N.J. As increased tolerance to uracilpyridine herbicides is a generaltrait wished to be inherited into a wide variety of plants like maize,wheat, rye, oat, triticale, rice, barley, soybean, peanut, cotton,rapeseed and canola, manihot, pepper, sunflower and tagetes, solanaceousplants like potato, tobacco, eggplant, and tomato, Vicia species, pea,alfalfa, bushy plants (coffee, cacao, tea), Salix species, trees (oilpalm, coconut), perennial grasses, and forage crops, these crop plantsare also preferred target plants for a genetic engineering as onefurther embodiment of the present invention. In a preferred embodiment,the plant is a crop plant. Forage crops include, but are not limited to,Wheatgrass, Canarygrass, Bromegrass, Wildrye Grass, Bluegrass,Orchardgrass, Alfalfa, Salfoin, Birdsfoot Trefoil, Alsike Clover, RedClover, and Sweet Clover.

In one embodiment of the present invention, transfection of a mutatedPPO polynucleotide into a plant is achieved by Agrobacterium mediatedgene transfer. One transformation method known to those of skill in theart is the dipping of a flowering plant into an Agrobacteria solution,wherein the Agrobacteria contains the mutated PPO nucleic acid, followedby breeding of the transformed gametes. Agrobacterium mediated planttransformation can be performed using for example the GV3101(pMP90)(Koncz and Schell, 1986, Mol. Gen. Genet. 204:383-396) or LBA4404(Clontech) Agrobacterium tumefaciens strain. Transformation can beperformed by standard transformation and regeneration techniques(Deblaere et al., 1994, Nucl. Acids. Res. 13:4777-4788; Gelvin, StantonB. and Schilperoort, Robert A, Plant Molecular Biology Manual, 2ndEd.—Dordrecht : Kluwer Academic Publ., 1995.— in Sect., Ringbuc ZentraleSignatur: BT11-P ISBN 0-7923-2731-4; Glick, Bernard R. and Thompson,John E., Methods in Plant Molecular Biology and Biotechnology, BocaRaton: CRC Press, 1993 360 S., ISBN 0-8493-5164-2). For example,rapeseed can be transformed via cotyledon or hypocotyl transformation(Moloney et al., 1989, Plant Cell Report 8:238-242; De Block et al.,1989, Plant Physiol. 91:694-701). Use of antibiotics for Agrobacteriumand plant selection depends on the binary vector and the Agrobacteriumstrain used for transformation. Rapeseed selection is normally performedusing kanamycin as selectable plant marker. Agrobacterium mediated genetransfer to flax can be performed using, for example, a techniquedescribed by Mlynarova et al., 1994, Plant Cell Report 13:282-285.Additionally, transformation of soybean can be performed using forexample a technique described in European Patent No. 0424 047, U.S. Pat.No. 5,322,783, European Patent No. 0397 687, U.S. Pat. No. 5,376,543, orU.S. Pat. No. 5,169,770. Transformation of maize can be achieved byparticle bombardment, polyethylene glycol mediated DNA uptake, or viathe silicon carbide fiber technique. (See, for example, Freeling andWalbot “The maize handbook” Springer Verlag: New York (1993) ISBN3-540-97826-7). A specific example of maize transformation is found inU.S. Pat. No. 5,990,387, and a specific example of wheat transformationcan be found in PCT Application No. WO 93/07256.

According to the present invention, the introduced mutated PPOpolynucleotide may be maintained in the plant cell stably if it isincorporated into a non-chromosomal autonomous replicon or integratedinto the plant chromosomes. Alternatively, the introduced mutated PPOpolynucleotide may be present on an extra-chromosomal non-replicatingvector and be transiently expressed or transiently active. In oneembodiment, a homologous recombinant microorganism can be createdwherein the mutated PPO polynucleotide is integrated into a chromosome,a vector is prepared which contains at least a portion of an PPO geneinto which a deletion, addition, or substitution has been introduced tothereby alter, e.g., functionally disrupt, the endogenous PPO gene andto create a mutated PPO gene. To create a point mutation via homologousrecombination, DNA-RNA hybrids can be used in a technique known aschimeraplasty (Cole-Strauss et al., 1999, Nucleic Acids Research27(5):1323-1330 and Kmiec, 1999, Gene therapy American Scientist87(3):240-247). Other homologous recombination procedures in Triticumspecies are also well known in the art and are contemplated for useherein.

In the homologous recombination vector, the mutated PPO gene can beflanked at its 5′ and 3′ ends by an additional nucleic acid molecule ofthe PPO gene to allow for homologous recombination to occur between theexogenous mutated PPO gene carried by the vector and an endogenous PPOgene, in a microorganism or plant. The additional flanking PPO nucleicacid molecule is of sufficient length for successful homologousrecombination with the endogenous gene. Typically, several hundreds ofbase pairs up to kilobases of flanking DNA (both at the 5′ and 3′ ends)are included in the vector (see e.g., Thomas, K. R., and Capecchi, M.R., 1987, Cell 51:503 for a description of homologous recombinationvectors or Strepp et al., 1998, PNAS, 95(8):4368-4373 for cDNA basedrecombination in Physcomitrella patens). However, since the mutated PPOgene normally differs from the PPO gene at very few amino acids, aflanking sequence is not always necessary. The homologous recombinationvector is introduced into a microorganism or plant cell (e.g., viapolyethylene glycol mediated DNA), and cells in which the introducedmutated PPO gene has homologously recombined with the endogenous PPOgene are selected using art-known techniques.

In another embodiment, recombinant microorganisms can be produced thatcontain selected systems that allow for regulated expression of theintroduced gene. For example, inclusion of a mutated PPO gene on avector placing it under control of the lac operon permits expression ofthe mutated PPO gene only in the presence of IPTG. Such regulatorysystems are well known in the art.

Another aspect of the invention pertains to host cells into which arecombinant expression vector of the invention has been introduced. Theterms “host cell” and “recombinant host cell” are used interchangeablyherein. It is understood that such terms refer not only to theparticular subject cell but they also apply to the progeny or potentialprogeny of such a cell. Because certain modifications may occur insucceeding generations due to either mutation or environmentalinfluences, such progeny may not, in fact, be identical to the parentcell, but are still included within the scope of the term as usedherein. A host cell can be any prokaryotic or eukaryotic cell. Forexample, a mutated PPO polynucleotide can be expressed in bacterialcells such as C. glutamicum, insect cells, fungal cells, or mammaliancells (such as Chinese hamster ovary cells (CHO) or COS cells), algae,ciliates, plant cells, fungi or other microorganisms like C. glutamicum.Other suitable host cells are known to those skilled in the art.

A host cell of the invention, such as a prokaryotic or eukaryotic hostcell in culture, can be used to produce (i.e., express) a mutated PPOpolynucleotide. Accordingly, the invention further provides methods forproducing mutated PPO polypeptides using the host cells of theinvention. In one embodiment, the method comprises culturing the hostcell of invention (into which a recombinant expression vector encoding amutated PPO polypeptide has been introduced, or into which genome hasbeen introduced a gene encoding a wild-type or mutated PPO polypeptide)in a suitable medium until mutated PPO polypeptide is produced. Inanother embodiment, the method further comprises isolating mutated PPOpolypeptides from the medium or the host cell. Another aspect of theinvention pertains to isolated mutated PPO polypeptides, andbiologically active portions thereof. An “isolated” or “purified”polypeptide or biologically active portion thereof is free of some ofthe cellular material when produced by recombinant DNA techniques, orchemical precursors or other chemicals when chemically synthesized. Thelanguage “substantially free of cellular material” includes preparationsof mutated PPO polypeptide in which the polypeptide is separated fromsome of the cellular components of the cells in which it is naturally orrecombinantly produced. In one embodiment, the language “substantiallyfree of cellular material” includes preparations of a mutated PPOpolypeptide having less than about 30% (by dry weight) of non-mutatedPPO material (also referred to herein as a “contaminating polypeptide”),more preferably less than about 20% of non-mutated PPO material, stillmore preferably less than about 10% of non-mutated PPO material, andmost preferably less than about 5% non-mutated PPO material.

When the mutated PPO polypeptide, or biologically active portionthereof, is recombinantly produced, it is also preferably substantiallyfree of culture medium, i.e., culture medium represents less than about20%, more preferably less than about 10%, and most preferably less thanabout 5% of the volume of the polypeptide preparation. The language“substantially free of chemical precursors or other chemicals” includespreparations of mutated PPO polypeptide in which the polypeptide isseparated from chemical precursors or other chemicals that are involvedin the synthesis of the polypeptide. In one embodiment, the language“substantially free of chemical precursors or other chemicals” includespreparations of a mutated PPO polypeptide having less than about 30% (bydry weight) of chemical precursors or non-mutated PPO chemicals, morepreferably less than about 20% chemical precursors or non-mutated PPOchemicals, still more preferably less than about 10% chemical precursorsor non-mutated PPO chemicals, and most preferably less than about 5%chemical precursors or non-mutated PPO chemicals. In preferredembodiments, isolated polypeptides, or biologically active portionsthereof, lack contaminating polypeptides from the same organism fromwhich the mutated PPO polypeptide is derived. Typically, suchpolypeptides are produced by recombinant expression of, for example, amutated PPO polypeptide in plants other than, or in microorganisms suchas C. glutamicum, ciliates, algae, or fungi.

In other aspects, a method for treating a plant of the present inventionis provided.

In some embodiments, the method comprises contacting the plant with anagronomically acceptable composition.

In another aspect, the present invention provides a method for preparinga descendent seed. The method comprises planting a seed of or capable ofproducing a plant of the present invention. In one embodiment, themethod further comprises growing a descendent plant from the seed; andharvesting a descendant seed from the descendent plant. In otherembodiments, the method further comprises applying a uracilpyridineherbicides herbicidal composition to the descendent plant.

In another embodiment, the invention refers to harvestable parts of thetransgenic plant according to the present invention. Preferably, theharvestable parts comprise the PPO nucleic acid or PPO protein of thepresent invention. The harvestable parts may be seeds, roots, leavesand/or flowers comprising the PPO nucleic acid or PPO protein or partsthereof. Preferred parts of soy plants are soy beans comprising the PPOnucleic acid or PPO protein.

In another embodiment, the invention refers to products derived from aplant according to the present invention, parts thereof or harvestableparts thereof. A preferred plant product is fodder, seed meal, oil, orseed-treatment-coated seeds. Preferably, the meal and/or oil comprisesthe mutated PPO nucleic acids or PPO proteins of the present invention.

In another embodiment, the invention refers to a method for theproduction of a product, which method comprises

-   -   a) growing the plants of the invention or obtainable by the        methods of invention and    -   b) producing said product from or by the plants of the invention        and/or parts, e.g. seeds, of these plants.

In a further embodiment the method comprises the steps

-   -   a) growing the plants of the invention,    -   b) removing the harvestable parts as defined above from the        plants and    -   c) producing said product from or by the harvestable parts of        the invention.

The product may be produced at the site where the plant has been grown,the plants and/or parts thereof may be removed from the site where theplants have been grown to produce the product. Typically, the plant isgrown, the desired harvestable parts are removed from the plant, iffeasible in repeated cycles, and the product made from the harvestableparts of the plant. The step of growing the plant may be performed onlyonce each time the methods of the invention is performed, while allowingrepeated times the steps of product production e.g. by repeated removalof harvestable parts of the plants of the invention and if necessaryfurther processing of these parts to arrive at the product. It is alsopossible that the step of growing the plants of the invention isrepeated and plants or harvestable parts are stored until the productionof the product is then performed once for the accumulated plants orplant parts. Also, the steps of growing the plants and producing theproduct may be performed with an overlap in time, even simultaneously toa large extend or sequentially. Generally the plants are grown for sometime before the product is produced.

In one embodiment the products produced by said methods of the inventionare plant products such as, but not limited to, a foodstuff, feedstuff,a food supplement, feed supplement, fiber, cosmetic and/orpharmaceutical Foodstuffs are regarded as compositions used fornutrition and/or for supplementing nutrition. Animal feedstuffs andanimal feed supplements, in particular, are regarded as foodstuffs.

In another embodiment the inventive methods for the production are usedto make agricultural products such as, but not limited to, plantextracts, proteins, amino acids, carbohydrates, fats, oils, polymers,vitamins, and the like.

It is possible that a plant product consists of one or more agriculturalproducts to a large extent.

As described above, the present invention teaches compositions andmethods for increasing the PPO-inhibiting tolerance of a crop plant orseed as compared to a wild-type variety of the plant or seed. In apreferred embodiment, the PPO-inhibiting tolerance of a crop plant orseed is increased such that the plant or seed can withstand auracilpyridine herbicide application of preferably approximately 1-1000g ai ha⁻¹, more preferably 1-200 g ai ha⁻¹, even more preferably 5-150 gai ha⁻¹, and most preferably 10-100 g ai ha⁻¹. As used herein, to“withstand” a uracilpyridine herbicide application means that the plantis either not killed or only moderately injured by such application. Itwill be understood by the person skilled in the art that the applicationrates may vary, depending on the environmental conditions such astemperature or humidity, and depending on the chosen kind of herbicide(active ingredient ai).

Furthermore, the present invention provides methods that involve the useof at least one uracilpyridine herbicide, optionally in combination withone or more herbicidal compounds B, and, optionally, a safener C, asdescribed in detail supra.

In these methods, the uracilpyridine herbicide can be applied by anymethod known in the art including, but not limited to, seed treatment,soil treatment, and foliar treatment. Prior to application, theuracilpyridine herbicide can be converted into the customaryformulations, for example solutions, emulsions, suspensions, dusts,powders, pastes and granules. The use form depends on the particularintended purpose; in each case, it should ensure a fine and evendistribution of the compound according to the invention.

By providing plants having increased tolerance to uracilpyridineherbicide, a wide variety of formulations can be employed for protectingplants from weeds, so as to enhance plant growth and reduce competitionfor nutrients. A uracilpyridine herbicide can be used by itself forpre-emergence, post-emergence, pre-planting, and at-planting control ofweeds in areas surrounding the crop plants described herein, or auracilpyridine herbicide formulation can be used that contains otheradditives. The uracilpyridine herbicide can also be used as a seedtreatment. Additives found in a uracilpyridine herbicide formulationinclude other herbicides, detergents, adjuvants, spreading agents,sticking agents, stabilizing agents, or the like. The uracilpyridineherbicide formulation can be a wet or dry preparation and can include,but is not limited to, flowable powders, emulsifiable concentrates, andliquid concentrates. The uracilpyridine herbicide and herbicideformulations can be applied in accordance with conventional methods, forexample, by spraying, irrigation, dusting, or the like.

Suitable formulations are described in detail in PCT/EP2009/063387 andPCT/EP2009/063386, which are incorporated herein by reference.

It should also be understood that the foregoing relates to preferredembodiments of the present invention and that numerous changes may bemade therein without departing from the scope of the invention. Theinvention is further illustrated by the following examples, which arenot to be construed in any way as imposing limitations upon the scopethereof.

On the contrary, it is to be clearly understood that resort may be hadto various other embodiments, modifications, and equivalents thereof,which, after reading the description herein, may suggest themselves tothose skilled in the art without departing from the spirit of thepresent invention and/or the scope of the appended claims.

EXAMPLES

Uracilpyridine 1 ethyl2-[[3-[2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)pyrimidin-1-yl]phenoxy]-2-pyridyl]oxy]acetate Uracilpyridine 2 ethyl2-[[3-[[3-chloro-5-fluoro-6-[3-methyl-2,6-dioxo-4-(trifluoromethyl)pyrimidin-1-yl]-2-pyridyl]oxy]-2-pyridyl]oxy]acetate Uracilpyridine 32-[[3-[[3-chloro-5-fluoro-6-[3-methyl-2,6-dioxo-4-(trifluoromethyl)pyrimidin-1-yl]-2-pyridyl]oxy]-2-pyridyl]oxy]acetic acid Uracilpyridine 4 ethyl2-[2-[[3-chloro-5-fluoro-6-[3-methyl-2,6-dioxo-4-(trifluoromethyl)pyrimidin-1-yl]-2-pyridyl]oxy]phenoxy]acetate Uracilpyridine 52-[2-[[3-chloro-5-fluoro-6-[3-methyl-2,6-dioxo-4-(trifluoromethyl)pyrimidin-1-yl]-2-pyridyl]oxy]phenoxy]acetic acid Uracilpyridine 6 ethyl2-[2-[[3-bromo-6-[3-methyl-2,6-dioxo-4-(trifluoromethyl)pyrimidin-1-yl]-2-pyridyl]oxy]phenoxy]acetate Uracilpyridine 7 ethyl2-[2-[[3-chloro-5-fluoro-6-[3-methyl-2,6-dioxo-4-(trifluoromethyl)pyrimidin-1-yl]-2-pyridyl]oxy]-4-fluoro-phenoxy]acetate Uracilpyridine 8 ethyl2-[2-[[3,5-difluoro-6-[3-methyl-2,6-dioxo-4-(trifluoromethyl)pyrimidin-1-yl]-2-pyridyl]oxy]phenoxy]acetate Uracilpyridine 92-[2-[[3,5-difluoro-6-[3-methyl-2,6-dioxo-4-(trifluoromethyl)pyrimidin-1-yl]-2-pyridyl]oxy]phenoxy]acetic acid Uracilpyridine 102-[2-[[3-chloro-5-fluoro-6-[3-methyl-2,6-dioxo-4-(trifluoromethyl)pyrimidin-1-yl]-2-pyridyl]oxy]phenoxy]-N-methylsulfonyl-acetamide Uracilpyridine 11 ethyl2-[[3-[[3-chloro-6-[3,5-dimethyl-2,6-dioxo-4-(trifluoromethyl)pyrimidin-1-yl]-5-fluoro-2-pyridyl]oxy]-2-pyridyl]oxy]acetate Uracilpyridine 12 ethyl2-[2-[[3-chloro-6-[3,5-dimethyl-2,6-dioxo-4-(trifluoromethyl)pyrimidin-1-yl]-5-fluoro-2-pyridyl]oxy]phenoxy]acetate Uracilpyridine 13 allyl2-[[3-[[3-chloro-5-fluoro-6-[3-methyl-2,6-dioxo-4-(trifluoromethyl)pyrimidin-1-yl]-2-pyridyl]oxy]-2-pyridyl]oxy]acetate Uracilpyridine 14 prop-2-ynyl2-[[3-[[3-chloro-5-fluoro-6-[3-methyl-2,6-dioxo-4-(trifluoromethyl)pyrimidin-1-yl]-2-pyridyl]oxy]-2-pyridyl]oxy]acetate Uracilpyridine 15cyclopropylmethyl 2-[[3-[[3-chloro-5-fluoro-6-[3-methyl-2,6-dioxo-4-(trifluoromethyl)pyrimidin-1-yl]-2-pyridyl]oxy]-2-pyridyl]oxy]acetateUracilpyridine 16 2,2-difluoroethyl2-[[3-[[3-chloro-5-fluoro-6-[3-methyl-2,6-dioxo-4-(trifluoromethyl)pyrimidin-1-yl]-2-pyridyl]oxy]-2-pyridyl]oxy]acetateUracilpyridine 17 isobutyl2-[[3-[[3-chloro-5-fluoro-6-[3-methyl-2,6-dioxo-4-(trifluoromethyl)pyrimidin-1-yl]-2-pyridyl]oxy]-2-pyridyl]oxy]acetate Uracilpyridine 18(2-ethoxy-2-oxo-ethyl)2-[[3-[[3-chloro-5-fluoro-6-[3-methyl-2,6-dioxo-4-(trifluoromethyl)pyrimidin-1-yl]-2-pyridyl]oxy]-2-pyridyl]oxy]acetateUracilpyridine 19 2-methoxyethyl2-[[3-[[3-chloro-5-fluoro-6-[3-methyl-2,6-dioxo-4-(trifluoromethyl)pyrimidin-1-yl]-2-pyridyl]oxy]-2-pyridyl]oxy]acetateUracilpyridine 202-[[3-[[3-chloro-5-fluoro-6-[3-methyl-2,6-dioxo-4-(trifluoromethyl)pyrimidin-1-yl]-2-pyridyl]oxy]-2-pyridyl]oxy]-N-methylsulfonyl-acetamide Uracilpyridine 21methyl2-[2-[[3-chloro-5-fluoro-6-[3-methyl-2,6-dioxo-4-(trifluoromethyl)pyrimidin-1-yl]-2-pyridyl]oxy]phenoxy]acetate Uracilpyridine 22 ethyl2-[2-[[3-bromo-5-fluoro-6-[3-methyl-2,6-dioxo-4-(trifluoromethyl)pyrimidin-1-yl]-2-pyridyl]oxy]phenoxy]acetate

Example 1: Site-Directed Mutagenesis PPO

All nucleic acid coding sequence and all single and double mutantsencoding a herbicide tolerant PPO polypeptides are synthesized andcloned by Geneart (Geneart AG, Regensburg, Germany). Rational designmutants are synthesized by Geneart. Random PPO gene libraries aresynthesized by Geneart. Plasmids are isolated from E. coli TOP10 byperforming a plasmid minpreparation and confirmed by DNA sequencing.

Example 2: Expression and Purification of Recombinant Wildtype andMutant PPO

(Taken from: Franck E. Dayan, Pankaj R. Daga, Stephen O. Duke, Ryan M.Lee, Patrick J. Tranel, Robert J. Doerksen. Biochemical and structuralconsequences of aglycine deletion in the α-8 helix of protoporphyrinogenoxidase. Biochimica et Biophysica Acta 1804 (2010), 1548-56) Clones inpRSET vector are transformed into BL21(DE3)-pLysS strain of E. coli.Cells are grown in 250 mL of LB with 100 μgmL-1 of carbenicillin,shaking overnight at 37° C. Cultures are diluted in 1 L of LB withantibiotic and grown at 37° C. shaking for 2 h, induced with 1 mM IPTGand grown at 25° C. shaking for 5 more hours. The cells are harvested bycentrifugation at 1600×g, washed with 0.09% NaCl, and stored at −80° C.Cells are lysed using a French press at 140 MPa in 50 mM sodiumphosphate pH 7.5, 1 M NaCl, 5 mM imidazole, 5% glycerol, and 1 pg mL-1leupeptin. Following lysis, 0.5 U of benzonase (Novagen, EMD Chemicals,Inc., Gibbstown, N.J.) and PMSF (final concentration of 1 mM) are added.Cell debris is removed by centrifugation at 3000×g. His-tagged PPOproteins are purified on a nickel activated Hitrap Chelating HP column(GE Healthcare Bio-Sciences Corp., Piscataway, N.J.) equilibrated with20 mM sodium phosphate pH 8.0, 50 mM NaCl, 5 mM imidazole, 5 mM MgCl2,0.1 mM EDTA, and 17% glycerol. PPO is eluted with 250 mM imidazole. Theactive protein is desalted on a PD-10 column (GE Healthcare Bio-SciencesCorp., Piscataway, N.J.) equilibrated with a 20 mM sodium phosphatebuffer, pH 7.5, 5 mM MgCl2, 1 mM EDTA and 17% glycerol. Each litre ofculture provided approximately 10 mg of pure PPO, which is stored at−20° C. until being used in assays.

Example 3: PPO Enzyme Assay (Non-Recombinant)

PPO protein (EC 1.3.3.4) is extracted from coleoptiles or shoots (150 gfresh weight) of dark-grown corn, black nightshade, morning glory, andvelvetleaf seedlings as described previously (Grossmann et al. 2010).Before harvesting, the seedlings are allowed to green for 2 hours in thelight in order to achieve the highest specific enzyme activities in thethylakoid fractions at low chlorophyll concentrations. At highchlorophyll concentrations significant quenching of fluorescence occurs,which limits the amount of green thylakoids that can be used in thetest. Plant materials are homogenized in the cold with a Braun blenderusing a fresh-weight-to-volume ratio of 1:4. Homogenization bufferconsisted of tris(hydroxymethyl)aminomethane (Tris)-HCl (50 mM; pH 7.3),sucrose (0.5 M), magnesium chloride (1 mM), ethylenediaminetetraaceticacid (EDTA) (1 mM) and bovine serum albumin (2 g L⁻¹). After filtrationthrough four layers of Miracloth, crude plastid preparations areobtained after centrifugation at 10 000 x g for 5 min and resuspensionin homogenization buffer before centrifugation at 150×g for 2 min toremove crude cell debris. The supernatant is centrifuged at 4000×g for15 min and the pellet fraction is resuspended in 1 ml of a buffercontaining Tris-HCl (50 mM; pH 7.3), EDTA (2 mM), leupeptin (2 μM),pepstatin (2 μM) and glycerol (200 ml L⁻¹) and stored at −80° C. untiluse. Protein is determined in the enzyme extract with bovine serumalbumin as a standard. PPO activity is assayed fluorometrically bymonitoring the rate of Proto formation from chemically reducedprotoporphyrinogen IX under initial velocity conditions. The assaymixture consisted of Tris-HCl (100 mM; pH 7.3), EDTA (1 mM),dithiothreitol (5 mM), Tween 80 (0.085%), protoporphyrinogen IX (2 μM),and 40 pg extracted protein in a total volume of 200 pl. The reaction isinitiated by addition of substrate protoporphyrinogen IX at 22° C. Theuracilpyridines disclosed SUPRA, and photosynthesis inhibitor diuron asnegative control are prepared in dimethyl sulfoxide (DMSO) solution (0.1mM concentration of DMSO in the assay) and added to the assay mixture inconcentrations of 0.005 μM to 5 μM before incubation. Fluorescence ismonitored directly from the assay mixture using a POLARstarOptima/Galaxy (BMG) with excitation at 405 nm and emission monitored at630 nm. Non-enzymatic activity in the presence of heat-inactivatedextract is negligible. Inhibition of enzyme activity induced by theherbicide is expressed as percentage inhibition relative to untreatedcontrols. Molar concentrations of compound required for 50% enzymeinhibition (IC₅₀ values) are calculated by fitting the values to thedose-response equation using non-linear regression analysis.

Example 4: PPO Enzyme Assay (Recombinant)

Proto is purchased from Sigma-Aldrich (Milwaukee, Wis.). Protogen isprepared according to Jacobs and Jacobs (N.J. Jacobs, J. M. Jacobs,Assay for enzymatic protoporphyrinogen oxidation, a late step in hemesynthesis, Enzyme 28 (1982) 206-219). Assays are conducted in 100 mMsodium phosphate pH 7.4 with 0.1 mM EDTA, 0.1% Tween 20, 5 μM FAD, and500 mM imidazole. Dose-response curves with the uracilpyridinesdisclosed SUPRA, and photosynthesis inhibitor diuron as negativecontrol, and MC-15608 are obtained in the presence of 150 μM Protogen.The excitation and emission bandwidths are set at 1.5 and 30 nm,respectively. All assays are made in duplicates or triplicates andmeasured using a POLARstar Optima/Galaxy (BMG) with excitation at 405 nmand emission monitored at 630 nm. Molar concentrations of compoundrequired for 50% enzyme inhibition (IC₅₀ values) are calculated byfitting the values to the dose-response equation using non-linearregression analysis. The results are shown in Table x.

TABLE x Variant PPO Enzyme and IC50 (M) Wild Type Tolerance Based on SEQID NO: 1 PPO Enzyme Factor Compound (Amaranthus PPO2) IC50 (M) (R/S)Uracilpyridine R128A, F420V 2.80E−07 1.77E−10 1579 1 UracilpyridineR128A, F420V 1.62E−07 1.77E−10 915 1 Uracilpyridine R128A, F420M6.16E−08 1.77E−10 347 1 Uracilpyridine L397Q, F420V 2.26E−06 1.77E−1012739 1 Uracilpyridine L397Q, F420M 4.29E−07 1.77E−10 2418 1Uracilpyridine L397Q 2.38E−09 1.77E−10 13 1 Uracilpyridine F420V6.64E−08 1.77E−10 374 1 Uracilpyridine F420M 3.81E−08 1.77E−10 215 1Uracilpyridine F420M 4.69E−08 1.77E−10 265 1 Uracilpyridine R128A, F420V2.97E−07 1.73E−10 1718 4 Uracilpyridine R128A, F420M 6.94E−08 1.73E−10401 4 Uracilpyridine F420M 9.44E−09 1.73E−10 55 4 Uracilpyridine R128A,F420V 1.49E−07 1.87E−10 796 2 Uracilpyridine R128A, F420V 2.07E−071.87E−10 1105 2 Uracilpyridine R128A, F420M 9.74E−08 1.87E−10 521 2Uracilpyridine L397Q, F420V 2.56E−06 1.87E−10 13678 2 UracilpyridineL397Q, F420M 9.05E−07 1.87E−10 4843 2 Uracilpyridine L397Q 1.29E−091.87E−10 7 2 Uracilpyridine F420V 1.06E−07 1.87E−10 567 2 UracilpyridineF420M 4.57E−08 1.87E−10 244 2 Uracilpyridine F420M 7.76E−08 1.87E−10 4152 Uracilpyridine R128A, F420V 2.25E−06 4.96E−10 4531 8 UracilpyridineF420M 6.91E−08 4.96E−10 139 8 Uracilpyridine R128A, F420M 1.67E−062.12E−10 7879 10  Uracilpyridine L397E, F420M 6.51E−06 2.12E−10 3071410  Uracilpyridine R128A, F420M 1.14E−07 2.12E−10 536 12  UracilpyridineR128A, F420M 9.18E−08 2.18E−10 421 13  Uracilpyridine R128A, F420M1.58E−07 2.34E−10 675 14  Uracilpyridine R128A, F420M 1.25E−07 2.48E−10503 19  Uracilpyridine R128A, F420M 4.29E−08 2.20E−10 195 15 Uracilpyridine R128A, F420M 8.90E−08 1.75E−10 508 16  UracilpyridineR128A, F420M 4.61E−08 1.13E−10 406 17  Uracilpyridine R128A, F420M1.16E−07 1.54E−10 753 18 

Example 5: Engineering PPO-Derivative Herbicide Tolerant Plants HavingWildtype or Mutated PPO Sequences

PPO-derivative herbicide tolerant soybean (Glyceine max), plants areproduced by a method as described by Olhoft et al. (US patent2009/0049567). For transformation of soybean or Arabidopsis thaliana,Wildtype or Mutated PPO sequences encoding herbicide tolerant PPOpolypeptides are cloned with standard cloning techniques as described inSambrook eta. (Molecular cloning (2001) Cold Spring Harbor LaboratoryPress) in a binary vector containing resistance marker gene cassette(AHAS) and mutated PPO sequence (marked as GOI) in between ubiquitinpromoter (PcUbi) and nopaline synthase terminator (NOS) sequence. Forcorn transformation, Wildtype or Mutated PPO sequences are cloned withstandard cloning techniques as described in Sambrook et a. (Molecularcloning (2001) Cold Spring Harbor Laboratory Press) in a binary vectorcontaining resistance marker gene cassette (AHAS) and mutated PPOsequence (marked as GOI) in between corn ubiquitin promoter (ZmUbi) andnopaline synthase terminator (NOS) sequence. Binary plasmids areintroduced to Agrobacterium tumefaciens for plant transformation.Plasmid constructs are introduced into soybean's axillary meristem cellsat the primary node of seedling explants via Agrobacterium-mediatedtransformation. After inoculation and co-cultivation with Agrobacteria,the explants are transferred to shoot introduction media withoutselection for one week. The explants are subsequently transferred to ashoot induction medium with 1-3 μM imazapyr (Arsenal) for 3 weeks toselect for transformed cells. Explants with healthy callus/shoot pads atthe primary node are then transferred to shoot elongation mediumcontaining 1-3 μM imazapyr until a shoot elongated or the explant died.Transgenic plantlets are rooted, subjected to TaqMan analysis for thepresence of the transgene, transferred to soil and grown to maturity ingreenhouse. Plant transformation vector constructs containing mutatedPPO sequences are introduced into maize immature embryos viaAgrobacterium-mediated transformation according to the procedureoutlined in Peng et a.(WO2006/136596). .

Transformed cells are selected in selection media supplemented with0.5-1.5 μM imazethapyr for 3-4 weeks. Transgenic plantlets areregenerated on plant regeneration media and rooted afterwards.Transgenic plantlets are subjected to TaqMan analysis for the presenceof the transgene before being transplanted to potting mixture and grownto maturity in greenhouse. Arabidopsis thaliana are transformed withwildtype or mutated PPO sequences by floral dip method as described byMcElver and Singh (WO 2008/124495). Transgenic Arabidopsis plants aresubjected to TaqMan analysis for analysis of the number of integrationloci. Transformation of Oryza sativa(rice) are done by protoplasttransformation as described by Peng et a. (U.S. Pat. No. 6,653,529) T0or T1 transgenic plants of soybean, corn, and rice containing mutatedPPO sequences are tested for improved tolerance to PPO-derivedherbicides in greenhouse studies and mini-plot studies with theuracilpyridines disclosed SUPRA, and photosynthesis inhibitor diuron asnegative control.

Example 6: Tissue Culture Conditions

An in vitro tissue culture mutagenesis assay has been developed toisolate and characterize plant tissue (e.g., maize, rice tissue) that istolerant to protoporphyrinogen oxidase inhibiting herbicides, e.g. theuracilpyridines disclosed SUPRA, and photosynthesis inhibitor diuron asnegative control). The assay utilizes the somaclonal variation that isfound in in vitro tissue culture. Spontaneous mutations derived fromsomaclonal variation can be enhanced by treatment with a chemicalmutagen (e.g. Ethyl methanesulfonate, N-ethyl-N-nitrosourea,N-Nitroso-N-methylurea) and subsequent selection in a stepwise manner,on increasing concentrations of herbicide.

The present invention provides tissue culture conditions for encouraginggrowth of friable, embryogenic maize or rice callus that is regenerable.Calli are initiated from rice cultivar Indica (Indica I). Seeds aresurface sterilized in 70% ethanol for approximately 1 min followed by20% commercial Clorox bleach for 20 minutes. Seeds are rinsed withsterile water and plated on R001 M media. The ingredient lists for themedia tested are presented in Table y.

TABLE y Ingredients Supplier R001M R025M R026M R327M R008S N6 SaltsPhytotech   4 g/L   4 g/L 4.3 g/L 4.3 g/L 3.25 g/L N6 vitamins Phytotech1X 1X 1X 1X Maltose VWR  30 g/L  30 g/L  30 g/L  30 g/L Casamino Acid BD0.3 g/L 0.3 g/L   2 g/L Proline Sigma 2.9 g/L 0.5 g/L 2,4-D ICN   2 mg/LMES Sigma 0.5 g/L 0.5 g/L 0.5 g/L 0.5 g/L  0.5 g/L MS Salts Phytotech MSVitamins Phytotech Sorbitol Sigma  30 g/L Sucrose Sigma   20 g/LNicotinic Acid Sigma  0.5 mg/L Pyridoxine HCL Sigma  0.5 mg/L ThiamineHCL Sigma   1 mg/L Myo-inositol Sigma  0.1 g/L

R001M callus induction media is selected after testing numerousvariations. Cultures are kept in the dark at 30° C. Embryogenic callusis subcultured to fresh media after 10-14 days.

Example 7: Selection of Herbicide-Tolerant Calli

Once tissue culture conditions are determined, further establishment ofselection conditions are established through the analysis of tissuesurvival in kill curves with saflufenacil, trifludimoxazin,sulfentrazone, and the uracilpyridines disclosed SUPRA, andphotosynthesis inhibitor diuron as negative control. Carefulconsideration of accumulation of the herbicide in the tissue, as well asits persistence and stability in the cells and the culture media isperformed. Through these experiments, a sub-lethal dose has beenestablished for the initial selection of mutated material. After theestablishment of the starting dose of uracilpyridines disclosed SUPRA,and photosynthesis inhibitor diuron as negative control in selectionmedia, the tissues are selected in a step-wise fashion by increasing theconcentration of the PPO inhibitor with each transfer until cells arerecovered that grew vigorously in the presence of toxic doses. Theresulting calli are further subcultured every 3-4 weeks to R001M withselective agent. Over 26,000 calli are subjected to selection for 4-5subcultures until the selective pressure is above toxic levels asdetermined by kill curves and observations of continued culture.Alternatively, liquid cultures initiated from calli in MS711R with slowshaking and weekly subcultures. Once liquid cultures are established,selection agent is added directly to the flask at each subculture.Following 2-4 rounds of liquid selection, cultures are transferred tofilters on solid R001M media for further growth.

Example 8: Regeneration of Plants

Tolerant tissue, e.g. rice tissue, is regenerated and characterizedmolecularly for PPO gene, e.g. Oryza sative PPO2 sequence mutationsand/or biochemically for altered PPO activity in the presence of theselective agent. In addition, genes involved directly and/or indirectlyin tetrapyrrole biosynthesis and/or metabolism pathways are alsosequenced to characterize mutations. Finally, enzymes that change thefate (e.g. metabolism, translocation, transportation) are also sequenceto characterized mutations. Following herbicide selection, calli areregenerated using a media regime of R025M for 10-14 days, R026M for ca.2 weeks, R327M until well formed shoots are developed, and R008S untilshoots are well rooted for transfer to the greenhouse. Regeneration iscarried out in the light. No selection agent is included duringregeneration. Once strong roots are established, M0 regenerants aretransplant to the greenhouse in square or round pots. Transplants aremaintained under a clear plastic cup until they are adapted togreenhouse conditions. The greenhouse is set to a day/night cycle of 27°C./21° C. (80° F./70° F.) with 600 W high pressure sodium lightssupplementing light to maintain a 14 hour day length. Plants are wateredaccording to need, depending in the weather and fertilized daily.

Example 9: Sequence Analysis

Leaf tissue is collected from clonal plants separated for transplantingand analyzed as individuals. Genomic DNA is extracted using a ChloropureNucleic acid extraction kit (Agencourt, U.S. Pat. Nos. 5,898,071;5,705,628; 6,534,262) as directed by the manufacturer. Isolated DNA isPCR amplified using the appropriate forward and reverse primer. PCRamplification is performed using LongAmp HotStart Taq DNA Polymerase Mix(New England Biolabs) using thermocycling program as follows: 94° C. for30 sec, followed by 35 cycles (94° C., 30 sec; 54° C., 30 sec; 65° C.,300 sec), 10 min at 65° C.

PCR products are verified for concentration and fragment size viaagarose gel electrophoresis. Dephosphorylated PCR products are analyzedby direct sequence using the PCR primers (Genewiz or GenScript).Chromatogram trace files (.scf) are analyzed for mutation relative tothe wild-type gene using Sequencher (Gene Codes) or Vector NTI Advance10™(Invitrogen). Based on sequence information, mutations are identifiedin several individuals. Sequence analysis is performed on therepresentative chromatograms and corresponding alignment with defaultsettings and edited to call secondary peaks.

Example 10: Demonstration of Herbicide-Tolerance

T0 or T1 transgenic plant of soybean, corn, Canola varieties and ricecontaining PPO1 and or PPO2 sequences are tested for improved toleranceto herbicides in greenhouse studies and mini-plot studies with theuracilpyridines disclosed SUPRA, and photosynthesis inhibitor diuron asnegative control. For the pre-emergence treatment, the herbicides areapplied directly after sowing by means of finely distributing nozzles.The containers are irrigated gently to promote germination and growthand subsequently covered with transparent plastic hoods until the plantshave rooted. This cover causes uniform germination of the test plants,unless this has been impaired by the herbicides. For post emergencetreatment, the test plants are first grown to a height of 3 to 15 cm,depending on the plant habit, and only then treated with the herbicides.For this purpose, the test plants are either sown directly, and grown inthe same containers or they are first grown separately and transplantedinto the test containers a few days prior to treatment.

For testing of T0 plants, cuttings can be used. In the case of soybeanplants, an optimal shoot for cutting is about 7.5 to 10 cm tall, with atleast two nodes present. Each cutting is taken from the originaltransformant (mother plant) and dipped into rooting hormone powder(indole-3-butyric acid, IBA). The cutting is then placed in oasis wedgesinside a bio-dome. Wild type cuttings are also taken simultaneously toserve as controls. The cuttings are kept in the bio-dome for 5-7 daysand then transplanted to pots and then acclimated in the growth chamberfor two more days. Subsequently, the cuttings are transferred to thegreenhouse, acclimated for approximately 4 days, and then subjected tospray tests as indicated. Depending on the species, the plants are keptat 10-25° C. or 20-35° C. The test period extends over 3 weeks. Duringthis time, the plants are tended and their response to the individualtreatments is evaluated. Herbicide injury evaluations are taken at 2 and3 weeks after treatment. Plant injury is rated on a scale of 0% to 100%,0% being no injury and 100% being complete death.

Transgenic Arabidopsis thaliana plants are assayed for improvedtolerance to the uracilpyridines disclosed SUPRA, in 48-well plates.Therefore, T2 seeds are surface sterilized by stirring for 5 min inethanol+water (70+30 by volume), rinsing one time with ethanol+water(70+30 by volume) and two times with sterile, deionized water. The seedsare resuspended in 0.1% agar dissolved in water (w/v) Four to five seedsper well are plated on solid nutrient medium consisting of half-strengthmurashige skoog nutrient solution, pH 5.8 (Murashige and Skoog (1962)Physiologia Plantarum 15: 473-497). Compounds are dissolved indimethylsulfoxid (DMSO) and added to the medium prior solidification(final DMSO concentration 0.1%). Multi well plates are incubated in agrowth chamber at 22° C., 75% relative humidity and 110 μmolPhot*m⁻²*s⁻¹ with 14: 10 h light: dark photoperiod. Growth inhibition isevaluated seven to ten days after seeding in comparison to wild typeplants. The results are shown in Table i)

Compound Gene Species Source Construct Name Tolerance Factor*Uracilpyridine 1 Amaranthus tuberculatus AMATU_PPO2_WT 6 Uracilpyridine1 Amaranthus tuberculatus AMATU_PPO2_F420M 110 Uracilpyridine 1Amaranthus tuberculatus AMATU_PPO2_L397D 50 Uracilpyridine 1 Amaranthustuberculatus AMATU_PPO2_L397D_F420V 41 Uracilpyridine 1 Amaranthustuberculatus AMATU_PPO2_R128A_F420M 50 Uracilpyridine 1 Amaranthustuberculatus AMATU_PPO2_R128A_F420V 75 Uracilpyridine 1 Arabidopsisthaliana ARBTH_PPO1_WT 50 Uracilpyridine 1 Arabidopsis thalianaARBTH_PPO1_S305L_Y426M 250 Uracilpyridine 3 Escherichia coliAMATU_PPO2_TP_hemG 1600 Uracilpyridine 9 Escherichia coliAMATU_PPO2_TP_hemG 1600 Uracilpyridine 4 Escherichia coliAMATU_PPO2_TP_hemG 810000 Uracilpyridine 5 Escherichia coliAMATU_PPO2_TP_hemG 1400 Uracilpyridine 2 Escherichia coliAMATU_PPO2_TP_hemG 6400 Uracilpyridine 8 Escherichia coliAMATU_PPO2_TP_hemG 8202 Transgenic T2 Arabidopsis plants harboring PPOinhibitor tolerance trait in lab based germination assay.

Additionally, transgenic T2 Arabidopsi plants are tested for improvedtolerance to herbicides in greenhouse studies with the uracilpyridinesas disclosed SUPRA, and photosynthesis inhibitor diuron as negativecontrol. Results are shown in table ii), table iii), and FIG. 1.

TABLE ii Transgenic T2 Arabidopsis plants, sprayed post in thegreenhouse with the indicated amount of PPO inhibitor + 1% (v/v) MSO.Evaluation performed 14 Days After Treatment (DAT) and is shown asinjury (%) relative to non-transgenic treated plants. ARBTH WT MC24 -non-transgenic ARBTH_PPO1_WT AMATU_PPO2_WTALOMY_PPO2_TP_AMATU_PPO2_R128M_F420I AMATU_PPO2_R128M_F420I Compoundgai/ha / Q Q R K Uracilpyridine 2 200 100 75 70 100 100 45 58 80 100 50100 45 18 30 100 100 100 10 100 100 100 5 100 100 100 1 100 15 23Uracilpyridine 3 80 100 30 100 100 100 10 100 98 100 5 100 83 80 1 88 1048 Uracilpyridine 4 200 100 80 73 100 100 60 58 80 100 50 100 40 30 30100 100 100 10 100 100 100 5 100 99 88 1 100 33 25 Uracilpyridine 5 80100 30 100 100 100 10 100 99 100 5 100 90 90 1 100 45 28 Uracilpyridine1 200 100 84 75 100 100 92 73 50 100 60 60 Uracilpyridine 10 200 100 50Uracilpyridine 6 200 100 50 Uracilpyridine 7 200 100 50 Uracilpyridine 880 100 30 100 100 100 10 100 55 100 5 100 30 55 1 88 10 10Uracilpyridine 9 80 100 30 100 98 100 10 100 70 100 5 100 50 68 1 85 1038 Uracilpyridine 10 80 100 30 100 100 100 10 100 100 100 5 100 98 100 1100 50 58 AMATU_PPO2_R128A_F420M AMATU_PPO2_TP_hemG AMATU_PPO2_TP_hemGALOMY_PPO2_R137L_F438V ALOMY_PPO2_R137L_F438V Compound gai/ha Q R R F GUracilpyridine 2 200 65 35 30 23 20 100 15 40 33 18 10 80 50 10 55 28 180 30 10 5 1 Uracilpyridine 3 80 30 10 5 1 Uracilpyridine 4 200 60 65 208 100 60 38 20 15 80 50 55 30 8 8 30 10 5 1 Uracilpyridine 5 80 30 10 51 Uracilpyridine 1 200 75 53 65 28 100 60 63 33 75 50 100 55 60 20 5Uracilpyridine 10 200 10 5 100 8 0 50 0 0 Uracilpyridine 6 200 18 0 1000 0 50 0 0 Uracilpyridine 7 200 13 8 100 18 0 50 0 0 Uracilpyridine 8 8030 10 5 1 Uracilpyridine 9 80 30 10 5 1 Uracilpyridine 10 80 30 10 5 1AMATU_PPO2_R128A_F420V AMATU_PPO2_R128A_F420V AMATU_PPO2_L397E_F420VAMATU_PPO2_L397E_F420V ARBTH_PPO1_S305L_Y426M Compound gai/ha A D D L OUracilpyridine 2 200 100 80 45 50 30 33 10 0 5 0 1 Uracilpyridine 3 8013 30 49 10 0 5 0 1 Uracilpyridine 4 200 100 80 95 50 30 0 10 0 5 0 1Uracilpyridine 5 80 73 30 68 10 0 5 0 1 Uracilpyridine 1 200 100 50 100Uracilpyridine 10 200 68 88 13 20 100 53 78 5 53 50 38 30 0 8Uracilpyridine 6 200 30 28 8 15 100 43 38 0 0 50 0 0 0 0 Uracilpyridine7 200 70 75 10 33 100 50 65 0 0 50 13 33 0 0 Uracilpyridine 8 80 0 30 010 0 5 0 1 Uracilpyridine 9 80 0 30 0 10 0 5 0 1 Uracilpyridine 10 80 9930 99 10 8 5 10 1

TABLE iii Transgenic T2 Arabidopsis plants, sprayed post in thegreenhouse with the indicated amount of PPO inhibitor + 1% (v/v) MSO.Evaluation performed 14 Days After Treatment (DAT) and is shown asinjury (%) relative to non-transgenic treated plants. Compound g ai/haARBTH WT MC 24 (non-transgenic) ALOMY_PPO2_R137L_F438MALOMY_PPO2_R137L_F438M Uracilpyridine 100 100 0 0 2 50 100 0 0Uracilpyridine 100 100 0 0 4 50 100 0 0 Uracilpyridine 100 100 20 0 1 50100 0 0 Compound g ai/ha ALOMY_PPO2_R137L_F438M ALOMY_PPO2_R137L_F438MALOMY_PPO2_R137L_F438V Uracilpyridine 100 0 0 0 2 50 0 0 0Uracilpyridine 100 0 0 0 4 50 0 0 10 Uracilpyridine 100 0 0 0 1 50 0 0 5Compound g ai/ha ALOMY_PPO2_R137L_F438V ALOMY_PPO2_R137L_F438VALOMY_PPO2_R137L_F438V Uracilpyridine 100 0 0 0 2 50 0 0 0Uracilpyridine 100 10 10 10 4 50 0 0 0 Uracilpyridine 100 25 35 40 1 5050 15 0 Compound g ai/ha AMATU_PPO2_L397E_F420V AMATU_PPO2_L397E_F420VAMATU_PPO2_L397E_F420V Uracilpyridine 100 0 0 0 2 50 0 0 0Uracilpyridine 100 0 30 0 4 50 0 10 0 Uracilpyridine 100 0 35 55 1 50 010 0 Compound g ai/ha AMATU_PPO2_L397E_F420V AMATU_PPO2_L397E_F420MAMATU_PPO2_L397E_F420M Uracilpyridine 100 0 10 35 2 50 15 0 0Uracilpyridine 100 0 15 35 4 50 10 0 25 Uracilpyridine 100 0 15 30 1 5035 0 10 Compound g ai/ha AMATU_PPO2_L397E_F420M AMATU_PPO2_L397E_F420MAMATU_PPO2_L397Q_F420V Uracilpyridine 100 0 20 80 2 50 0 0 45Uracilpyridine 100 60 20 80 4 50 0 0 60 Uracilpyridine 100 60 55 85 1 5015 40 40 Compound g ai/ha ARBTH WT MC 24 (non-transgenic)AMATU_PPO2_L397Q_F420V AMATU_PPO2_R128A_F420L Uracilpyridine 100 100 6560 2 50 100 0 0 Uracilpyridine 100 100 — 10 4 50 100 — 0 Uracilpyridine100 100 65 60 1 50 100 75 65 Compound g ai/ha AMATU_PPO2_R128A_F420LAMATU_PPO2_R128A_F420L AMATU_PPO2_R128A_F420L Uracilpyridine 100 35 1530 2 50 0 0 15 Uracilpyridine 100 65 20 20 4 50 10 0 0 Uracilpyridine100 90 95 80 1 50 75 5 75 Compound g ai/ha AMATU_PPO2_R128A_F420IAMATU_PPO2_R128A_F420I AMATU_PPO2_R128A_F420I Uracilpyridine 100 65 6565 2 50 0 45 65 Uracilpyridine 100 65 50 55 4 50 0 50 40 Uracilpyridine100 65 80 95 1 50 70 75 60 Compound g ai/ha AMATU_PPO2_R128A_F420IAMATU_PPO2_R128A_F420M AMATU_PPO2_R128A_F420M Uracilpyridine 100 30 0 652 50 0 0 0 Uracilpyridine 100 65 25 65 4 50 50 0 15 Uracilpyridine 10060 35 80 1 50 60 55 65 Compound g ai/ha AMATU_PPO2_R128A_F420MAMATU_PPO2_R128A_F420M AMATU_PPO2_R128A F420V Uracilpyridine 100 30 0 852 50 30 0 0 Uracilpyridine 100 40 45 15 4 50 25 30 75 Uracilpyridine 10065 65 95 1 50 25 40 90 Compound g ai/ha AMATU_PPO2_R128A F420VAMATU_PPO2_R128A F420V AMATU_PPO2_R128A F420V Uracilpyridine 100 70 2565 2 50 0 20 0 Uracilpyridine 100 75 25 40 4 50 70 60 75 Uracilpyridine100 98 95 80 1 50 55 65 95

Example 11: Demonstration of Herbicide Tolerance in MutagenizedNon-Transgenic Rice

Selected mutants are transferred to pots and grown in the greenhouse forseed production. The resulting M1 progeny are screened for the presenceand zygosity of tolerance conferring mutations in the OsPPO2 gene, e.g.mutated OsPPO2 polypeptides as shown in SEQ ID Nos: 628, 629, 630, 631,632, 633, 634, 635, 636, or 637. M1 plants containing a homozygous inthe OsPPO2 gene are kept for seed production to generate a stable,homozygous, herbicide tolerant line. Homozygous lines ca. 2 weeks oldare sprayed using a track sprayer with uracilpyridine 2 oruracilpyridine 4 supplemented with 0.1% methylated seed oil. Oncesprayed, plants are kept on drought conditions for 24 hours before beingwatered and fertilized again. Sprayed plants are photographed and ratedfor herbicide injury at 3 days and 7 days treatment. The results areshown in FIGS. 1 to 4.

Example 12: Herbicide Selection Using Tissue Culture

Media is selected for use and kill curves developed as specified above.For selection, different techniques are utilized. Either a step wiseselection is applied, or an immediate lethal level of herbicide isapplied. In either case, all of the calli are transferred for each newround of selection. Selection is 4-5 cycles of culture with 3-5 weeksfor each cycle. Cali are placed onto nylon membranes to facilitatetransfer (200 micron pore sheets, Biodesign, Saco, Me.). Membranes arecut to fit 100×20 mm Petri dishes and are autoclaved prior to use 25-35calli (average weight/calli being 22 mg) are utilized in every plate. Inaddition, one set of calli are subjected to selection in liquid culturemedia with weekly subcultures followed by further selection onsemi-solid media. Mutant lines are selected using the uracilpyridines asdisclosed SUPRA, and photosynthesis inhibitor diuron as negativecontrol. Efficiencies of obtaining mutants is high either based on apercentage of calli that gave rise to a regenerable, mutant line or thenumber of lines as determined by the gram of tissue utilized.

Example 13: Maize Whole Plant Transformation and PPO Inhibitor ToleranceTesting

Immature embryos are transformed according to the procedure outlined inPeng et al. (WO2006/136596). Plants are tested for the presence of theT-DNA by Taqman analysis with the target being the nos terminator whichis present in all constructs. Healthy looking plants are sent to thegreenhouse for hardening and subsequent spray testing. The plants areindividually transplanted into MetroMix 360 soil in 4″ pots. Once in thegreenhouse (day/night cycle of 27° C./21° C. with 14 hour day lengthsupported by 600 W high pressure sodium lights), they are allowed togrow for 14 days. T0 or T1 plants are sprayed with a treatment of theuracilpyridines as disclosed SUPRA and photosynthesis inhibitor diuronas negative control. Herbicide injury evaluations are taken at 7, 14 and21 days after treatment. Herbicide injury evaluations are taken 2, 7, 14and 21 days post-spray to look for injury to new growth points andoverall plant health. The top survivors are transplanted into gallonpots filled with MetroMix 360 for seed production.

Transgenic T2 Corn plants harbouring PPO inhibitor tolerance trait, weresprayed post with the indicated amount of uracilpyridine+1% (v/v) MSO.Evaluation performed 14 Days After Treatment (DAT) and shown as injury(0-9) relative to non-transgenic treated plants. Injury Scale: 0-9, 0=noinjury, 9=maximum injury. Note: segregating lines. The results are shownin the following Table and in FIGS. 7 and 8.

Corn Trial R128A, R128A, R128A, J553 Rate F420I F420L F420L non Compound(g/ha) Event 1 Event 2 Event 3 transgenic Check 0 0 1 5 1 1 1 6 1 2 0 61% MSO 0 0 0 1 1 0 0 2 1 1 1 1 Uracilpyridine 25 1 0 1 9 2 0 1 0 9 1 0 09 Uracilpyridine 50 0 1 0 9 2 1 1 0 9 0 1 1 9 Uracilpyridine 100 1 1 0 92 0 1 1 9 1 1 1 9 Uracilpyridine 25 0 0 0 9 4 0 0 1 7 0 0 0 7Uracilpyridine 50 0 1 1 9 4 1 0 0 7 0 1 0 9 Uracilpyridine 100 1 0 1 9 40 1 0 9 0 1 0 9

Transgenic T3Maize plants harboring a PPO inhibitor tolerance traitsprayed post in the field at the V3 leaf stage with 100 g/ha of PPO inh.2+1% (v/v) MSO. Evaluation performed 2 and 12 Days After Treatment (DAT)and is shown as injury (%) relative to non-transgenic treated plants.Pictures taken 2 DAT.

Plant Injury (%) J553/TR5753 Non- AMATU_PPO2_ AMATU_PPO2_ DAT transgenicR128A_F420L R128A_F420I 2 95 0 0 12 100 0 0

Example 14: Soybean Transformation and PPO Inhibitor Tolerance Testing

Soybean cv Jake is transformed as previously described by Siminszky etal., Phytochem Rev. 5:445-458 (2006). After regeneration, transformantsare transplanted to soil in small pots, placed in growth chambers (16 hrday/8 hr night; 25° C. day/23° C. night; 65% relative humidity; 130-150microE m-2 s-1) and subsequently tested for the presence of the T-DNAvia Taqman analysis. After a few weeks, healthy, transgenic positive,single copy events are transplanted to larger pots and allowed to growin the growth chamber. An optimal shoot for cutting is about 3-4 inchestall, with at least two nodes present. Each cutting is taken from theoriginal transformant (mother plant) and dipped into rooting hormonepowder (indole-3-butyric acid, IBA). The cutting is then placed in oasiswedges inside a bio-dome. The mother plant is taken to maturity in thegreenhouse and harvested for seed. Wild type cuttings are also takensimultaneously to serve as negative controls. The cuttings are kept inthe bio-dome for 5-7 days and then transplanted to 3 inch pots and thenacclimated in the growth chamber for two more days. Subsequently, thecuttings are transferred to the greenhouse, acclimated for approximately4 days prior to spray. T0 or 2-week old T1 plants are sprayed with atreatment of the uracilpyridines as disclosed SUPRA and photosynthesisinhibitor diuron as negative control. Herbicide injury evaluations aretaken at 2, 7, 14 and 21 days after treatment.

Transgenic T2 or T3 Soybean plants harbouring PPO inhibitor tolerancetrait, were sprayed post in the greenhouse with the indicated amount ofuracilpyridine+1% (v/v) MSO. Evaluation performed 7 Days After Treatment(DAT) and shown as injury (0-9) relative to non-transgenic treatedplants. Injury Scale: 0-9, 0=no injury, 9=maximum injury. Note:segregating lines.

R128A, R128A, L397E, L397E, L397Q, Jake Rate F420L F420I F420V F420MF420M non Compound (g/ha) Event 1 Event 2 Event 3 Event 4 Event 5transgenic Uracilpyridine 25 1 1 2 1 1 9 1 1 1 1 2 2 9 1 * 1 1 2 9 1 9 11 1 9 Uracilpyridine 50 1 1 9 2 1 9 1 1 * 1 0 2 9 1 * 1 1 1 9 1 3 2 1 29 Uracilpyridine 100 1 1 1 1 3 9 1 1 2 1 2 2 9 1 * 9 * * 9 4 1 9 1 3 9Uracilpyridine 200 1 1 9 4 3 9 1 1 1 2 1 3 9 1 1 9 2 * 9 1 1 1 2 4 9 1%MSO 1 * 1 1 1 3 1 * 2 1 2 2 1 1 1 2 2 2 2 * 1 1 1 3 Check 1 * 0 1 0 1 00 1 1 2 0 0 * * 1 * 1 1 * 2 1 * 1

Transgenic T2 or T3 Soybean plants harbouring PPO inhibitor tolerancetrait, were sprayed post with the indicated amount of uracilpyridine+1%(v/v) MSO. Evaluation performed 14 Days After Treatment (DAT) and shownas injury (0-9) relative to non-transgenic treated plants. Injury Scale:0-9, 0=no injury, 9=maximum injury. Note: segregating lines. The resultsare shown in the following Table and in FIGS. 7 and 8.

Soybean Trial Rate L397E, F420V L397E, F420M L397Q, F420M Jake Compound(g/ha) Event 1 Event 2 Event 3 non transgenic Check 0 9 9 9 0 0 2 9 0 21 9 1% MSO 0 0 0 1 0 0 0 1 0 0 0 1 Uracilpyridine 25 0 0 0 9 2 0 0 9 9 00 3 9 Uracilpyridine 50 0 0 3 9 2 0 0 9 9 0 0 1 9 Uracilpyridine 100 0 01 9 2 0 0 3 9 0 0 2 9 Uracilpyridine 25 0 0 1 9 4 0 0 9 9 0 0 0 9Uracilpyridine 50 0 0 9 9 4 0 0 9 9 0 0 3 9 Uracilpyridine 100 0 0 3 9 40 0 4 9 0 1 3 9

Transgenic T4 Soybean plants harbouring PPO inhibitor tolerance trait,were sprayed post with the indicated amount of uracilpyridine+1% (v/v)MSO. Evaluation performed 7 Days After Treatment (DAT) and shown asinjury (0-9) relative to non-transgenic treated plants. Injury Scale:0-9, 0=no injury, 9=maximum injury. Asterisks indicates plants that didnot germinate. Results are also shown in FIGS. 9 through 12.

R128A + R128A + L397E + L397E + L397Q + Jake F420L F420I F420V F420MF420M non- Compound Rate (g/ha) Event 1 Event 2 Event 3 Event 4 Event 5transgenic Uracilpyridine 10 25 0 1 1 0 3 9 1 0 1 1 * 9 0 2 0 0 3 9 0 10 0 5 9 1 1 * 0 * * 0 1 * 0 3 9 Uracilpyridine 10 50 1 1 * 0 4 9 1 2 1 14 9 0 1 * 0 4 9 1 2 * 0 4 9 0 2 0 0 4 9 1 2 1 1 4 9 Uracilpyridine 10100 2 2 * 1 9 1 2 0 2 4 9 2 2 0 1 * 9 2 3 0 1 5 9 2 3 1 0 5 9 2 3 * 1 *9 Uracilpyridine 20 25 2 2 0 0 4 9 0 2 1 0 3 9 1 2 0 1 * 9 0 2 * 0 3 9 12 0 0 * 9 2 1 * 0 3 9 Uracilpyridine 20 50 3 3 0 0 * 9 3 3 0 1 * 9 2 3 00 3 9 1 2 1 1 4 9 2 3 1 0 4 9 2 3 0 0 4 9 Uracilpyridine 20 100 3 4 *0 * 9 4 4 0 0 4 9 5 4 0 1 * 9 4 * 1 4 9 5 4 0 1 7 9 * 4 2 1 * 9Uracilpyridine 21 25 0 0 0 0 3 9 1 1 0 0 2 9 1 1 * 0 2 9 1 1 0 0 3 9 11 * 0 * 9 1 1 * 1 2 9 Uracilpyridine 21 50 1 2 0 0 3 9 2 2 * 0 * 9 1 1 00 3 9 1 2 0 0 3 9 2 2 0 1 3 9 1 2 0 1 * 9 Uracilpyridine 21 100 2 3 * 03 9 1 3 * 0 3 9 4 2 0 0 * 9 2 3 2 0 3 9 2 2 0 0 3 9 2 3 0 1 * 9Uracilpyridine 22 25 0 1 * 1 * 9 0 0 0 0 1 9 0 0 0 0 * 9 1 1 0 0 1 9 0 20 0 2 9 1 1 1 1 1 9 Uracilpyridine 22 50 1 0 0 1 3 9 1 0 0 0 3 9 1 3 0 23 9 1 2 0 1 2 9 2 2 * 0 * 9 1 2 * 1 1 9 Uracilpyridine 22 100 1 2 * 0 *9 1 3 0 0 4 9 1 1 1 0 4 9 1 2 0 1 * 9 2 2 0 1 4 9 2 3 1 0 4 9

Transgenic T3 Soybean plants harboring a PPO inhibitor tolerance trait,sprayed post in the field at the V3 leaf stage with 100 g/ha of PPO inh.2+1% (v/v) MSO. Evaluation performed 2 and 12 Days After Treatment (DAT)and is shown as injury (%) relative to non-transgenic treated plants.Pictures taken 2 DAT.

Plant Injury (%) Jake Non- AMATU_PPO2_R128A, AMATU_PPO2_L397E,AMATU_PPO2_L397E, AMATU_PPO2_L397Q, EXP transgenic F420I F420V F420MF420M DAT PPO 92 10 0 5 5 2 Inh. 2 PPO 100 5 0 0 0 12 Inh. 2

The following gives a definition of the injury scores measured above:

Score Description of injury 0 No Injury 1 Minimal injury, only a fewpatches of leaf injury or chlorosis. 2 Minimal injury with slightlystronger chlorosis. Overall growth points remain undamaged. 3 Slightlystronger injury on secondary leaf tissue, but primary leaf and growthpoints are still undamaged. 4 Overall plant morphology is slightlydifferent, some chlorosis and necrosis in secondary growth points andleaf tissue. Stems are intact. Regrowth is highly probable within 1week. 5 Overall plant morphology is clearly different, some chlorosisand necrosis on a few leaves and growth points, but primary growth pointis intact. Stem tissue is still green. Regrowth is highly probablywithin 1 week. 6 Strong injury can be seen on the new leaflet growth.Plant has a high probability to survive only through regrowth atdifferent growth points. Most of the leaves are chlorotic/ necrotic butstem tissue is still green. May have regrowth but with noticeableinjured appearance. 7 Most of the active growth points are necrotic.There may be a single growth point that could survive and may bepartially chlorotic or green and partially necrotic. Two leaves maystill be chlorotic with some green; the rest of the plant including stemis necrotic. 8 Plant will likely die, and all growth points arenecrotic. One leaf may still be chlorotic with some green. The remainderof the plant is necrotic. 9 Plant is dead.

1. A method for controlling undesired vegetation at a plant cultivationsite, the method comprising the steps of: a) providing, at said site, aplant that comprises at least one nucleic acid comprising a nucleotidesequence encoding a protoporphyrinogen oxidase (PPO) polypeptide whichis resistant or tolerant to a “PPO inhibiting herbicide”; b) applying tosaid site an effective amount of said herbicide, wherein the PPOinhibiting herbicide is a uracilpyridine of formula (I)

wherein the substituents have the following meanings: R¹ hydrogen, NH₂,C₁-C₆-alkyl or C₃-C₆-alkynyl; R² hydrogen, C₁-C₆-alkyl orC₁-C₆-haloalkyl; R³ hydrogen or C₁-C₆-alkyl; R⁴ H or halogen; R⁵halogen, CN, NO₂, NH₂, CF₃ or C(═S)NH₂; R⁶ H, halogen, CN, C₁-C₃-alkyl,C₁-C₃-haloalkyl, C₁-C₃-alkoxy, C₁-C₃-haloalkoxy, C₁-C₃-alkylthio,(C₁-C₃-alkyl)amino, di(C₁-C₃-alkyl)amino, C₁-C₃-alkoxy- C₁-C₃-alkyl,C₁-C₃-alkoxycarbonyl; R⁷ H, halogen, C₁-C₃-alkyl, C₁-C₃-alkoxy; R⁸ OR⁹,SR⁹, NR¹⁰R¹¹, NR⁹OR⁹, NR⁹S(O)₂R¹⁰ or NR⁹S(O)₂NR¹⁰R¹¹, wherein R⁹ ishydrogen, C₁-C₆-alkyl, C₃-C₆-alkenyl, C₃-C₆-alkynyl, C₁-C₆-haloalkyl,C₃-C₆-haloalkenyl, C₃-C₆-haloalkynyl, C₁-C₆-cyanoalkyl, C₁-C₆-alkoxy-C₁-C₆-alkyl, C₁-C₆-alkoxy-C₁-C₆-alkoxy- C₁-C₆-alkyl, di(C₁-C₆-alkoxy)C₁-C₆-alkyl, C₁-C₆-haloalkoxy- C₁-C₆-alkyl, C₃-C₆-alkenyloxy-C₁-C₆-alkyl, C₃-C₆-haloalkenyloxy- C₁-C₆-alkyl, C₃-C₆-alkenyloxy-C₁-C₆-alkoxy- C₁-C₆-alkyl, C₁-C₆-alkylthio- C₁-C₆-alkyl,C₁-C₆-alkylsulfinyl- C₁-C₆-alkyl, C₁-C₆-alkylsulfonyl- C₁-C₆-alkyl,C₁-C₆-alkylcarbonyl- C₁-C₆-alkyl, C₁-C₆-alkoxycarbonyl- C₁-C₆-alkyl,C₁-C₆-haloalkoxycarbonyl- C₁-C₆-alkyl, C₃-C₆-alkenyloxycarbonyl-C₁-C₆-alkyl, C₃-C₆-alkynyloxycarbonyl- C₁-C₆-alkyl, amino,(C₁-C₆-alkyl)amino, di(C₁-C₆-alkyl)amino, (C₁-C₆-alkylcarbonyl)amino,amino- C₁-C₆-alkyl, (C₁-C₆-alkyl)amino- C₁-C₆-alkyl,di(C₁-C₆-alkyl)amino- C₁-C₆-alkyl, aminocarbonyl- C₁-C₆-alkyl,(C₁-C₆-alkyl)aminocarbonyl- C₁-C₆-alkyl, di(C₁-C₆-alkyl)aminocarbonyl-C₁-C₆-alkyl, —N═CR¹²R¹³, wherein R¹² and R¹³ independently of oneanother are H, C₁-C₄-alkyl or phenyl; C₃-C₆-cycloalkyl,C₃-C₆-cycloalkyl- C₁-C₆-alkyl, C₃-C₆-heterocyclyl, C₃-C₆-heterocyclyl-C₁-C₆-alkyl, phenyl, phenyl- C₁-C₄-alkyl or a 5- or 6 memberedheteroaryl, wherein each cycloalkyl, heterocyclyl, phenyl or heteroarylring can be substituted by one to four substituents selected from R¹⁴ ora 3- to 7-membered carbocyclus, which carbocyclus optionally has inaddition to carbon atoms one or two ring members selected from the groupconsisting of —N(R¹²)—, —N═N—, —C(═O)—, —O— and —S—, and whichcarbocyclus is optionally substituted with one to four substituentsselected from R¹⁴; wherein R¹⁴ is halogen, NO₂, CN, C₁-C₄-alkyl,C₁-C₄-halo-,alkyl, C₁-C₄-alkoxy or C₁-C₄-alkoxy-,carbonyl; R¹⁰, R¹¹independently of one another are R⁹, or together form a 3- to 7-memberedcarbocyclus, which carbocyclus optionally has in addition to carbonatoms one or two ring members selected from the group consisting of—N(R¹²)—, —N═N—, —C(═O)—, —O— and —S—, and which carbocyclus isoptionally substituted with one to four substituents selected from R¹⁴;n 1 to 3; Q CH₂, O, S, SO, SO₂, NH or (C₁-C₃-alkyl)N; W O or S; X NH,NCH₃, 0 or S; Y O or S; Z phenyl, pyridyl, pyridazinyl, pyrimidinyl orpyrazinyl, each of which is optionally substituted by 1 to 4substituents selected from the group consisting of halogen, CN,C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy, C₁-C₆-haloalkoxy; includingtheir agriculturally acceptable salts or derivatives, provided thecompounds of formula (I) have a carboxyl group, and wherein theeffective amount of said herbicide does not kill or inhibit the growthof the herbicide-tolerant plant of a).
 2. The method according to claim1, wherein the herbicide resistant or tolerant PPO polypeptide comprisesone or more of the following motifs 1, 2, and/or 3: a. Motif 1:SQ[N/K/H]KRYI, wherein the Arg at position 5 within said motif issubstituted by any other amino acid; b. Motif 2: TLGTLFSS, wherein theLeu at position 2, and/or the Gly at position 3, and/or the Leu atposition 5 within said motif is substituted by any other amino acid; c.Motif 3: [F/Y]TTF[V/I]GG, wherein the Phe at position 4 within saidmotif is substituted by any other amino acid.
 3. The method according toclaim 1, wherein the herbicide resistant or tolerant PPO polypeptidecomprises a variant of the amino acid sequence of SEQ ID NO: 1, 2, 3, 4,5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41,42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59,60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77,78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95,96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110,111, 112, 113, 114, 115, 116, 117, 577, 579, 581, 583, 585, 587, 589,591, 593, 595, 597, 599, 601, 603, 605, 607, 609, 611, 613, 615, 617,619, 621, 623, 625, 627, or 637, which variant comprises one or more ofthe following substitutions: a. the amino acid corresponding to Arg128of SEQ ID NO: 1 is substituted by any other amino acid. b. The aminoacid corresponding to Gly211 of SEQ ID NO: 1 is substituted by any otheramino acid c. the amino acid corresponding to Leu397 of SEQ ID NO: 1 issubstituted by any other amino acid. d. the amino acid corresponding toGly398 of SEQ ID NO: 1 is substituted by any other amino acid e. theamino acid corresponding to Leu400 of SEQ ID NO: 1 is substituted by anyother amino acid f. the amino acid corresponding to Phe420 of SEQ ID NO:1 is substituted by any other amino acid.
 4. The method according toclaim 1, wherein the herbicide resistant or tolerant PPO polypeptidecomprises the amino acid sequence of SEQ ID NO: 265, 266, 267, 268, 269,270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283,284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297,298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311,312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325,326, 327328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340,341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354,355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368,369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382,383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396,397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410,411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424,425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438,439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452,453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466,467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480,481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494,495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508,509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522,523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536,537, 538, 539, 540, 541, 542, 543, 544, 545, 546, 547, 548, 549, 550,551, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561, 562, 563, 564,565, or a variant thereof.
 5. The method according to claim 1, whereinthe herbicide resistant or tolerant PPO polypeptide comprises the aminoacid sequence of SEQ ID NO: 240, 241, 242, 243, 244, 245, 246, 247, 248,249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, or 262.6. The method according to claim 1, wherein the plant comprises at leastone additional heterologous nucleic acid comprising a nucleotidesequence encoding a herbicide tolerance enzyme.
 7. The method accordingto claim 1 wherein the uracilpyridine of formula (I) is applied inconjunction with one or more additional herbicides.